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image of Role of Glycolysis and Nitric Oxide Pathway Crosstalk in Macrophages in Atherosclerosis

Abstract

Atherosclerosis is a complex multifactorial process that occurs in the vascular wall over many years and is responsible for a number of major diseases that affect quality of life and prognosis. A growing body of evidence supports the notion that immune mechanisms underlie atherogenesis. Macrophages are considered one of the key participants in atherogenesis, but their role in this process is multifaceted, which is largely due to the peculiarities of their cellular metabolism. Glycolysis is not only an important metabolic pathway in macrophages, but is also associated with their immune functions. Glycolysis in macrophages has complex regulatory pathways and is cross-linked with nitric oxide, which together determine the immune function of these cells. Thus, the immune and metabolic links underlying atherogenesis are of research and clinical interest in terms of their potential therapeutic opportunities.

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References

  1. Balta A. Ceasovschih A. Șorodoc V. Dimitriadis K. Güzel S. Lionte C. Stătescu C. Sascău R. Mantzouranis E. Sakalidis A. Vlachakis P. Tsioufis P. Kordalis A. Tsiamis E. Tsioufis K. Șorodoc L. Broad electrocardiogram syndromes spectrum: From common emergencies to particular electrical heart disorders. J. Pers. Med. 2022 12 11 1754 10.3390/jpm12111754 36573711
    [Google Scholar]
  2. Gao D. Cai Y.S. Pan Y. Ma Q. Xie W. Editorial: Epidemiology and clinical researches in atherosclerosis and cardiovascular disease. Front. Cardiovasc. Med. 2023 10 1212269 10.3389/fcvm.2023.1212269 37260944
    [Google Scholar]
  3. Ceasovschih A. Mantzouranis E. Dimitriadis K. Sorodoc V. Vlachakis P.K. Karanikola A.E. Theofilis P. Koutsopoulos G. Drogkaris S. Andrikou I. Valatsou A. Lazaros G. Sorodoc L. Tsioufis K. Coronary artery thromboembolism as a cause of myocardial infarction with non-obstructive coronary arteries (MINOCA). Hellenic J. Cardiol. 2024 79 70 83 10.1016/j.hjc.2024.05.001 38825235
    [Google Scholar]
  4. Chen W. Li Z. Zhao Y. Chen Y. Huang R. Global and national burden of atherosclerosis from 1990 to 2019: Trend analysis based on the global burden of disease study 2019. Chin. Med. J. 2023 136 20 2442 2450 10.1097/CM9.0000000000002839 37677929
    [Google Scholar]
  5. Duggan J.P. Peters A.S. Trachiotis G.D. Antevil J.L. Epidemiology of coronary artery disease. Surg. Clin. North Am. 2022 102 3 499 516 10.1016/j.suc.2022.01.007 35671770
    [Google Scholar]
  6. Sarebanhassanabadi M. Mirjalili S.R. Vidal M.P. Kraemer A. Namayandeh S.M. Coronary artery disease incidence, risk factors, awareness, and medication utilization in a 10-year cohort study. BMC Cardiovasc. Disord. 2024 24 1 101 10.1186/s12872‑024‑03769‑3 38347457
    [Google Scholar]
  7. Horváth L. Németh N. Fehér G. Kívés Z. Endrei D. Boncz I. Epidemiology of peripheral artery disease: Narrative review. Life 2022 12 7 1041 10.3390/life12071041 35888129
    [Google Scholar]
  8. Libby P. Ridker P.M. Hansson G.K. Progress and challenges in translating the biology of atherosclerosis. Nature 2011 473 7347 317 325 10.1038/nature10146 21593864
    [Google Scholar]
  9. Kotlyarov S. Analysis of differentially expressed genes and signaling pathways involved in atherosclerosis and chronic obstructive pulmonary disease. Biomol. Concepts 2022 13 1 34 54 10.1515/bmc‑2022‑0001 35189051
    [Google Scholar]
  10. Kotlyarov S. The role of smoking in the mechanisms of development of chronic obstructive pulmonary disease and atherosclerosis. Int. J. Mol. Sci. 2023 24 10 8725 10.3390/ijms24108725 37240069
    [Google Scholar]
  11. Frangos S.G. Gahtan V. Sumpio B. Localization of atherosclerosis. Arch. Surg. 1999 134 10 1142 1149 10.1001/archsurg.134.10.1142 10522862
    [Google Scholar]
  12. Gusev E. Sarapultsev A. Atherosclerosis and inflammation: Insights from the theory of general pathological processes. Int. J. Mol. Sci. 2023 24 9 7910 10.3390/ijms24097910 37175617
    [Google Scholar]
  13. Benslaiman J.S. García G.U. Sebal L.A. Olaetxea J.R. Alloza I. Vandenbroeck K. Vicente B.A. Martín C. Pathophysiology of atherosclerosis. Int. J. Mol. Sci. 2022 23 6 3346 10.3390/ijms23063346 35328769
    [Google Scholar]
  14. Nordestgaard B.G. Triglyceride-rich lipoproteins and atherosclerotic cardiovascular disease. Circ. Res. 2016 118 4 547 563 10.1161/CIRCRESAHA.115.306249 26892957
    [Google Scholar]
  15. Cheng Q. Sun J. Zhong H. Wang Z. Liu C. Zhou S. Deng J. Research trends in lipid-lowering therapies for coronary heart disease combined with hyperlipidemia: A bibliometric study and visual analysis. Front. Pharmacol. 2024 15 1393333 10.3389/fphar.2024.1393333 38828451
    [Google Scholar]
  16. Rosenblit P.D. Lowering targeted atherogenic lipoprotein cholesterol goals for patients at “Extreme” ASCVD risk. Curr. Diab. Rep. 2019 19 12 146 10.1007/s11892‑019‑1246‑y 31754844
    [Google Scholar]
  17. Hou P. Fang J. Liu Z. Shi Y. Agostini M. Bernassola F. Bove P. Candi E. Rovella V. Sica G. Sun Q. Wang Y. Scimeca M. Federici M. Mauriello A. Melino G. Macrophage polarization and metabolism in atherosclerosis. Cell Death Dis. 2023 14 10 691 10.1038/s41419‑023‑06206‑z 37863894
    [Google Scholar]
  18. Strizova Z. Benesova I. Bartolini R. Novysedlak R. Cecrdlova E. Foley L.K. Striz I. M1/M2 macrophages and their overlaps – myth or reality? Clin. Sci. 2023 137 15 1067 1093 10.1042/CS20220531 37530555
    [Google Scholar]
  19. Chen S. Saeed A.F.U.H. Liu Q. Jiang Q. Xu H. Xiao G.G. Rao L. Duo Y. Macrophages in immunoregulation and therapeutics. Signal Transduct. Target. Ther. 2023 8 1 207 10.1038/s41392‑023‑01452‑1 37211559
    [Google Scholar]
  20. Mills C. M1 and M2 macrophages: Oracles of health and disease. Crit. Rev. Immunol. 2012 32 6 463 488 10.1615/CritRevImmunol.v32.i6.10 23428224
    [Google Scholar]
  21. Van den Bossche J. Baardman J. Otto N.A. van der Velden S. Neele A.E. van den Berg S.M. Martin L.R. Chen H.J. Boshuizen M.C.S. Ahmed M. Hoeksema M.A. de Vos A.F. de Winther M.P.J. Mitochondrial dysfunction prevents repolarization of inflammatory macrophages. Cell Rep. 2016 17 3 684 696 10.1016/j.celrep.2016.09.008 27732846
    [Google Scholar]
  22. Liu Y. Xu R. Gu H. Zhang E. Qu J. Cao W. Huang X. Yan H. He J. Cai Z. Metabolic reprogramming in macrophage responses. Biomark. Res. 2021 9 1 1 10.1186/s40364‑020‑00251‑y 33407885
    [Google Scholar]
  23. Rath M. Müller I. Kropf P. Closs E.I. Munder M. Metabolism via arginase or nitric oxide synthase: Two competing arginine pathways in macrophages. Front. Immunol. 2014 5 532 10.3389/fimmu.2014.00532 25386178
    [Google Scholar]
  24. Santhanam L. Lim H.K. Lim H.K. Miriel V. Brown T. Patel M. Balanson S. Ryoo S. Anderson M. Irani K. Khanday F. Costanzo D.L. Nyhan D. Hare J.M. Christianson D.W. Rivers R. Shoukas A. Berkowitz D.E. Inducible NO synthase dependent S-nitrosylation and activation of arginase1 contribute to age-related endothelial dysfunction. Circ. Res. 2007 101 7 692 702 10.1161/CIRCRESAHA.107.157727 17704205
    [Google Scholar]
  25. Gödecke A. Decking U.K.M. Ding Z. Hirchenhain J. Bidmon H.J. Gödecke S. Schrader J. Coronary hemodynamics in endothelial NO synthase knockout mice. Circ. Res. 1998 82 2 186 194 10.1161/01.RES.82.2.186 9468189
    [Google Scholar]
  26. Kalinin R.E. Suchkov I.A. Klimentova E.A. Shchulkin A.V. Povarov V.O. The role of different markers in progression of atherosclerotic lesions after open interventions for lower extremity peripheral artery disease. Kardiol. Serdechno Sosud. Khir. 2022 15 2 151 10.17116/kardio202215021151
    [Google Scholar]
  27. Zou M.H. Ullrich V. Peroxynitrite formed by simultaneous generation of nitric oxide and superoxide selectively inhibits bovine aortic prostacyclin synthase. FEBS Lett. 1996 382 1-2 101 104 10.1016/0014‑5793(96)00160‑3 8612727
    [Google Scholar]
  28. Bailey J.D. Diotallevi M. Nicol T. McNeill E. Shaw A. Chuaiphichai S. Hale A. Starr A. Nandi M. Stylianou E. McShane H. Davis S. Fischer R. Kessler B.M. McCullagh J. Channon K.M. Crabtree M.J. Nitric oxide modulates metabolic remodeling in inflammatory macrophages through TCA cycle regulation and itaconate accumulation. Cell Rep. 2019 28 1 218 230.e7 10.1016/j.celrep.2019.06.018 31269442
    [Google Scholar]
  29. Granger D.L. Lehninger A.L. Sites of inhibition of mitochondrial electron transport in macrophage-injured neoplastic cells. J. Cell Biol. 1982 95 2 527 535 10.1083/jcb.95.2.527 6292238
    [Google Scholar]
  30. Clementi E. Brown G.C. Feelisch M. Moncada S. Persistent inhibition of cell respiration by nitric oxide: Crucial role of S-nitrosylation of mitochondrial complex I and protective action of glutathione. Proc. Natl. Acad. Sci. 1998 95 13 7631 7636 10.1073/pnas.95.13.7631 9636201
    [Google Scholar]
  31. Cleeter M.W.J. Cooper J.M. Usmar D.V.M. Moncada S. Schapira A.H.V. Reversible inhibition of cytochrome c oxidase, the terminal enzyme of the mitochondrial respiratory chain, by nitric oxide. FEBS Lett. 1994 345 1 50 54 10.1016/0014‑5793(94)00424‑2 8194600
    [Google Scholar]
  32. Salvemini D. Mollace V. Pistelli A. Änggård E. Vane J. Cultured astrocytoma cells generate a nitric oxide-like factor from endogenous L-arginine and glyceryl trinitrate: Effect of E. coli lipopolysaccharide. Br. J. Pharmacol. 1992 106 4 931 936 10.1111/j.1476‑5381.1992.tb14437.x 1327394
    [Google Scholar]
  33. Wilcox J.N. Subramanian R.R. Sundell C.L. Tracey W.R. Pollock J.S. Harrison D.G. Marsden P.A. Expression of multiple isoforms of nitric oxide synthase in normal and atherosclerotic vessels. Arterioscler. Thromb. Vasc. Biol. 1997 17 11 2479 2488 10.1161/01.ATV.17.11.2479 9409218
    [Google Scholar]
  34. Moncada S. Palmer R.M. Higgs E.A. Nitric oxide: Physiology, pathophysiology, and pharmacology. Pharmacol. Rev. 1991 43 2 109 142 1852778
    [Google Scholar]
  35. Lamoke F. Mazzone V. Persichini T. Maraschi A. Harris M.B. Venema R.C. Colasanti M. Gliozzi M. Muscoli C. Bartoli M. Mollace V. Amyloid β peptide-induced inhibition of endothelial nitric oxide production involves oxidative stress-mediated constitutive eNOS/HSP90 interaction and disruption of agonist-mediated Akt activation. J. Neuroinflammation 2015 12 1 84 10.1186/s12974‑015‑0304‑x 25935150
    [Google Scholar]
  36. Bergmann S. Gerhards J.P. Schmitz A. Becker S.C. Stern M. No synthesis in immune-challenged locust hemocytes and potential signaling to the CNS. Insects 2021 12 10 951 10.3390/insects12100951 34680720
    [Google Scholar]
  37. Buttery L.D. Springall D.R. Chester A.H. Evans T.J. Standfield E.N. Parums D.V. Yacoub M.H. Polak J.M. Inducible nitric oxide synthase is present within human atherosclerotic lesions and promotes the formation and activity of peroxynitrite. Lab. Invest. 1996 75 1 77 85 8683942
    [Google Scholar]
  38. Depre C. Havaux X. Renkin J. Vanoverschelde J.L. Wijns W. Expression of inducible nitric oxide synthase in human coronary atherosclerotic plaque. Cardiovasc. Res. 1999 41 2 465 472 10.1016/S0008‑6363(98)00304‑6 10341846
    [Google Scholar]
  39. Ravalli S. Albala A. Ming M. Szabolcs M. Barbone A. Michler R.E. Cannon P.J. Inducible nitric oxide synthase expression in smooth muscle cells and macrophages of human transplant coronary artery disease. Circulation 1998 97 23 2338 2345 10.1161/01.CIR.97.23.2338 9639378
    [Google Scholar]
  40. Roussel B.D. Rupin A. Morel S.P. Fabiani J.N. Verbeuren T.J. Histochemical evidence for inducible nitric oxide synthase in advanced but non-ruptured human atherosclerotic carotid arteries. Histochem. J. 2000 32 1 41 51 10.1023/A:1003958312508 10805384
    [Google Scholar]
  41. Wilmes V. Kur I.M. Weigert A. Verhoff M.A. Gradhand E. Kauferstein S. iNOS expressing macrophages co-localize with nitrotyrosine staining after myocardial infarction in humans. Front. Cardiovasc. Med. 2023 10 1104019 10.3389/fcvm.2023.1104019 37063955
    [Google Scholar]
  42. Behr D. Rupin A. Fabiani J.N. Verbeuren T.J. Distribution and prevalence of inducible nitric oxide synthase in atherosclerotic vessels of long-term cholesterol-fed rabbits. Atherosclerosis 1999 142 2 335 344 10.1016/S0021‑9150(98)00254‑8 10030385
    [Google Scholar]
  43. Detmers P.A. Hernandez M. Mudgett J. Hassing H. Burton C. Mundt S. Chun S. Fletcher D. Card D.J. Lisnock J. Weikel R. Bergstrom J.D. Shevell D.E. Vosatka H.A. Sparrow C.P. Chao Y.S. Rader D.J. Wright S.D. Puré E. Deficiency in inducible nitric oxide synthase results in reduced atherosclerosis in apolipoprotein E-deficient mice. J. Immunol. 2000 165 6 3430 3435 10.4049/jimmunol.165.6.3430 10975863
    [Google Scholar]
  44. Kuhlencordt P.J. Chen J. Han F. Astern J. Huang P.L. Genetic deficiency of inducible nitric oxide synthase reduces atherosclerosis and lowers plasma lipid peroxides in apolipoprotein E-knockout mice. Circulation 2001 103 25 3099 3104 10.1161/01.CIR.103.25.3099 11425775
    [Google Scholar]
  45. Ozaki M. Kawashima S. Yamashita T. Hirase T. Namiki M. Inoue N. Hirata K. Yasui H. Sakurai H. Yoshida Y. Masada M. Yokoyama M. Overexpression of endothelial nitric oxide synthase accelerates atherosclerotic lesion formation in ApoE-deficient mice. J. Clin. Invest. 2002 110 3 331 340 10.1172/JCI0215215 12163452
    [Google Scholar]
  46. Chen J. Kuhlencordt P. Urano F. Ichinose H. Astern J. Huang P.L. Effects of chronic treatment with L-arginine on atherosclerosis in ApoE knockout and apoE/inducible NO synthase double-knockout mice. Arterioscler. Thromb. Vasc. Biol. 2003 23 1 97 103 10.1161/01.ATV.0000040223.74255.5A 12524231
    [Google Scholar]
  47. Gordon S. Martinez F.O. Alternative activation of macrophages: Mechanism and functions. Immunity 2010 32 5 593 604 10.1016/j.immuni.2010.05.007 20510870
    [Google Scholar]
  48. Dzik J.M. Evolutionary roots of arginase expression and regulation. Front. Immunol. 2014 5 544 10.3389/fimmu.2014.00544 25426114
    [Google Scholar]
  49. Edsfeldt A. Singh P. Matthes F. Tengryd C. Cavalera M. Bengtsson E. Dunér P. Volkov P. Karadimou G. Gisterå A. Melander O.M. Nilsson J. Sun J. Gonçalves I. Transforming growth factor-β2 is associated with atherosclerotic plaque stability and lower risk for cardiovascular events. Cardiovasc. Res. 2023 119 11 2061 2073 10.1093/cvr/cvad079 37200403
    [Google Scholar]
  50. Reifenberg K. Cheng F. Orning C. Crain J. Küpper I. Wiese E. Protschka M. Blessing M. Lackner K.J. Torzewski M. Overexpression of TGF-ß1 in macrophages reduces and stabilizes atherosclerotic plaques in ApoE-deficient mice. PLoS One 2012 7 7 e40990 10.1371/journal.pone.0040990 22829904
    [Google Scholar]
  51. Mallat Z. Gojova A. Fournigault M.C. Esposito B. Kamaté C. Merval R. Fradelizi D. Tedgui A. Inhibition of transforming growth factor-β signaling accelerates atherosclerosis and induces an unstable plaque phenotype in mice. Circ. Res. 2001 89 10 930 934 10.1161/hh2201.099415 11701621
    [Google Scholar]
  52. Rekhter M. Collagen synthesis in atherosclerosis: Too much and not enough. Cardiovasc. Res. 1999 41 2 376 384 10.1016/S0008‑6363(98)00321‑6 10341837
    [Google Scholar]
  53. Liu H. Chen Y.G. The interplay between TGF-β signaling and cell metabolism. Front. Cell Dev. Biol. 2022 10 846723 10.3389/fcell.2022.846723 35359452
    [Google Scholar]
  54. Yin X. Choudhury M. Kang J.H. Schaefbauer K.J. Jung M.Y. Andrianifahanana M. Hernandez D.M. Leof E.B. Hexokinase 2 couples glycolysis with the profibrotic actions of TGF-β. Sci. Signal. 2019 12 612 eaax4067 10.1126/scisignal.aax4067 31848318
    [Google Scholar]
  55. Zhou M.Y. Cheng M.L. Huang T. Hu R.H. Zou G.L. Li H. Zhang B.F. Zhu J.J. Liu Y.M. Liu Y. Zhao X.K. Transforming growth factor beta-1 upregulates glucose transporter 1 and glycolysis through canonical and noncanonical pathways in hepatic stellate cells. World J. Gastroenterol. 2021 27 40 6908 6926 10.3748/wjg.v27.i40.6908 34790014
    [Google Scholar]
  56. Kitagawa T. Masumi A. Akamatsu Y. Transforming growth factor-beta 1 stimulates glucose uptake and the expression of glucose transporter mRNA in quiescent Swiss mouse 3T3 cells. J. Biol. Chem. 1991 266 27 18066 18071 10.1016/S0021‑9258(18)55237‑6 1917944
    [Google Scholar]
  57. Awad K. Kakkola L. Julkunen I. High glucose increases lactate and induces the transforming growth factor Beta-Smad 1/5 atherogenic pathway in primary human macrophages. Biomedicines 2024 12 7 1575 10.3390/biomedicines12071575 39062148
    [Google Scholar]
  58. Gauthier T. Yao C. Dowdy T. Jin W. Lim Y.J. Patiño L.C. Liu N. Ohlemacher S.I. Bynum A. Kazmi R. Bewley C.A. Mitrovic M. Martin D. Morell R.J. Eckhaus M. Larion M. Tussiwand R. O’Shea J.J. Chen W. TGF-β uncouples glycolysis and inflammation in macrophages and controls survival during sepsis. Sci. Signal. 2023 16 797 eade0385 10.1126/scisignal.ade0385 37552767
    [Google Scholar]
  59. Oliver M.A. Davis X.D. Bohannon J.K. TGF-β macrophage reprogramming: A new dimension of macrophage plasticity. J. Leukoc. Biol. 2024 115 3 qiae001 10.1093/jleuko/qiae001 38197509
    [Google Scholar]
  60. Yang Z. Ming X.F. Functions of arginase isoforms in macrophage inflammatory responses: Impact on cardiovascular diseases and metabolic disorders. Front. Immunol. 2014 5 533 10.3389/fimmu.2014.00533 25386179
    [Google Scholar]
  61. Ming X.F. Rajapakse A.G. Yepuri G. Xiong Y. Carvas J.M. Ruffieux J. Scerri I. Wu Z. Popp K. Li J. Sartori C. Scherrer U. Kwak B.R. Montani J.P. Yang Z. Arginase II promotes macrophage inflammatory responses through mitochondrial reactive oxygen species, contributing to insulin resistance and atherogenesis. J. Am. Heart Assoc. 2012 1 4 e000992 10.1161/JAHA.112.000992 23130157
    [Google Scholar]
  62. Wang X.P. Zhang W. Liu X.Q. Wang W.K. Yan F. Dong W.Q. Zhang Y. Zhang M.X. Arginase I enhances atherosclerotic plaque stabilization by inhibiting inflammation and promoting smooth muscle cell proliferation. Eur. Heart J. 2014 35 14 911 919 10.1093/eurheartj/eht329 23999450
    [Google Scholar]
  63. Li Z. Wang L. Ren Y. Huang Y. Liu W. Lv Z. Qian L. Yu Y. Xiong Y. Arginase: Shedding light on the mechanisms and opportunities in cardiovascular diseases. Cell Death Discov. 2022 8 1 413 10.1038/s41420‑022‑01200‑4 36209203
    [Google Scholar]
  64. Feig J.E. Vengrenyuk Y. Reiser V. Wu C. Statnikov A. Aliferis C.F. Garabedian M.J. Fisher E.A. Puig O. Regression of atherosclerosis is characterized by broad changes in the plaque macrophage transcriptome. PLoS One 2012 7 6 e39790 10.1371/journal.pone.0039790 22761902
    [Google Scholar]
  65. Xiong Y. Yu Y. Montani J.P. Yang Z. Ming X.F. Arginase-II induces vascular smooth muscle cell senescence and apoptosis through p66Shc and p53 independently of its l-arginine ureahydrolase activity: Implications for atherosclerotic plaque vulnerability. J. Am. Heart Assoc. 2013 2 4 e000096 10.1161/JAHA.113.000096 23832324
    [Google Scholar]
  66. Rafnsson A. Matic L.P. Lengquist M. Mahdi A. Shemyakin A. Berne P.G. Hansson G.K. Gabrielsen A. Hedin U. Yang J. Pernow J. Endothelin-1 increases expression and activity of arginase 2 via ETB receptors and is co-expressed with arginase 2 in human atherosclerotic plaques. Atherosclerosis 2020 292 215 223 10.1016/j.atherosclerosis.2019.09.020 31606133
    [Google Scholar]
  67. Eligini S. Colli S. Habib A. Aldini G. Altomare A. Banfi C. Cyclooxygenase-2 glycosylation is affected by peroxynitrite in endothelial cells: Impact on enzyme activity and degradation. Antioxidants 2021 10 3 496 10.3390/antiox10030496 33806920
    [Google Scholar]
  68. Natarajan M. Konopinski R. Krishnan M. Roman L. Bera A. Hongying Z. Habib S.L. Mohan S. Inhibitor-κB kinase attenuates Hsp90-dependent endothelial nitric oxide synthase function in vascular endothelial cells. Am. J. Physiol. Cell Physiol. 2015 308 8 C673 C683 10.1152/ajpcell.00367.2014 25652452
    [Google Scholar]
  69. Pritchard K.A. Jr Ackerman A.W. Gross E.R. Stepp D.W. Shi Y. Fontana J.T. Baker J.E. Sessa W.C. Heat shock protein 90 mediates the balance of nitric oxide and superoxide anion from endothelial nitric-oxide synthase. J. Biol. Chem. 2001 276 21 17621 17624 10.1074/jbc.C100084200 11278264
    [Google Scholar]
  70. Fujii J. Osaki T. Involvement of nitric oxide in protecting against radical species and autoregulation of M1-polarized macrophages through metabolic remodeling. Molecules 2023 28 2 814 10.3390/molecules28020814 36677873
    [Google Scholar]
  71. De Santa F. Vitiello L. Torcinaro A. Ferraro E. The role of metabolic remodeling in macrophage polarization and its effect on skeletal muscle regeneration. Antioxid. Redox Signal. 2019 30 12 1553 1598 10.1089/ars.2017.7420 30070144
    [Google Scholar]
  72. Seneviratne A.N. Cole J.E. Goddard M.E. Park I. Mohri Z. Sansom S. Udalova I. Krams R. Monaco C. Low shear stress induces M1 macrophage polarization in murine thin-cap atherosclerotic plaques. J. Mol. Cell. Cardiol. 2015 89 Pt B 168 172 10.1016/j.yjmcc.2015.10.034 26523517
    [Google Scholar]
  73. Stöger J.L. Gijbels M.J.J. van der Velden S. Manca M. van der Loos C.M. Biessen E.A.L. Daemen M.J.A.P. Lutgens E. de Winther M.P.J. Distribution of macrophage polarization markers in human atherosclerosis. Atherosclerosis 2012 225 2 461 468 10.1016/j.atherosclerosis.2012.09.013 23078881
    [Google Scholar]
  74. Baardman J. Verberk S.G.S. Prange K.H.M. van Weeghel M. van der Velden S. Ryan D.G. Wüst R.C.I. Neele A.E. Speijer D. Denis S.W. Witte M.E. Houtkooper R.H. O’neill L.A. Knatko E.V. Kostova D.A.T. Lutgens E. de Winther M.P.J. Van den Bossche J. A defective pentose phosphate pathway reduces inflammatory macrophage responses during hypercholesterolemia. Cell Rep. 2018 25 8 2044 2052.e5 10.1016/j.celrep.2018.10.092 30463003
    [Google Scholar]
  75. Van den Bossche J. O’Neill L.A. Menon D. Macrophage immunometabolism: Where are we (Going)? Trends Immunol. 2017 38 6 395 406 10.1016/j.it.2017.03.001 28396078
    [Google Scholar]
  76. Nonnenmacher Y. Hiller K. Biochemistry of proinflammatory macrophage activation. Cell. Mol. Life Sci. 2018 75 12 2093 2109 10.1007/s00018‑018‑2784‑1 29502308
    [Google Scholar]
  77. Hard G.C. Some biochemical aspects of the immune macrophage. Br. J. Exp. Pathol. 1970 51 1 97 105 5434449
    [Google Scholar]
  78. Freemerman A.J. Johnson A.R. Sacks G.N. Milner J.J. Kirk E.L. Troester M.A. Macintyre A.N. Hicks G.P. Rathmell J.C. Makowski L. Metabolic reprogramming of macrophages: Glucose transporter 1 (GLUT-1)-mediated glucose metabolism drives a proinflammatory phenotype. J. Biol. Chem. 2014 289 11 7884 7896 10.1074/jbc.M113.522037 24492615
    [Google Scholar]
  79. Michl J. Ohlbaum D.J. Silverstein S.C. 2-Deoxyglucose selectively inhibits Fc and complement receptor-mediated phagocytosis in mouse peritoneal macrophages. I. Description of the inhibitory effect. J. Exp. Med. 1976 144 6 1465 1483 10.1084/jem.144.6.1465 1032901
    [Google Scholar]
  80. Diskin C. McDermott P.E.M. Metabolic modulation in macrophage effector function. Front. Immunol. 2018 9 270 10.3389/fimmu.2018.00270 29520272
    [Google Scholar]
  81. Luo W. Liu S. Zhang F. Zhao L. Su Y. Metabolic strategy of macrophages under homeostasis or immune stress in Drosophila. Mar. Life Sci. Technol. 2022 4 3 291 302 10.1007/s42995‑022‑00134‑1 37073169
    [Google Scholar]
  82. O’Neill L.A.J. Kishton R.J. Rathmell J. A guide to immunometabolism for immunologists. Nat. Rev. Immunol. 2016 16 9 553 565 10.1038/nri.2016.70 27396447
    [Google Scholar]
  83. Nagy C. Haschemi A. Time and demand are two critical dimensions of immunometabolism: The process of macrophage activation and the pentose phosphate pathway. Front. Immunol. 2015 6 164 10.3389/fimmu.2015.00164 25904920
    [Google Scholar]
  84. Grigorescu E.D. Lăcătușu C.M. Floria M. Cazac G.D. Onofriescu A. Ceasovschih A. Crețu I. Mihai B.M. Șorodoc L. Association of inflammatory and metabolic biomarkers with mitral annular calcification in type 2 diabetes patients. J. Pers. Med. 2022 12 9 1484 10.3390/jpm12091484 36143268
    [Google Scholar]
  85. Kazek M. Chodáková L. Lehr K. Strych L. Nedbalová P. McMullen E. Bajgar A. Opekar S. Šimek P. Moos M. Doležal T. Glucose and trehalose metabolism through the cyclic pentose phosphate pathway shapes pathogen resistance and host protection in Drosophila. PLoS Biol. 2024 22 5 e3002299 10.1371/journal.pbio.3002299 38713712
    [Google Scholar]
  86. Andrejeva G. Rathmell J.C. Similarities and distinctions of cancer and immune metabolism in inflammation and tumors. Cell Metab. 2017 26 1 49 70 10.1016/j.cmet.2017.06.004 28683294
    [Google Scholar]
  87. McDermott P.E.M. Curtis A.M. Goel G. Lauterbach M.A.R. Sheedy F.J. Gleeson L.E. van den Bosch M.W.M. Quinn S.R. Fernandez D.R. Johnston D.G.W. Jiang J. Israelsen W.J. Keane J. Thomas C. Clish C. Heiden V.M. Xavier R.J. O’Neill L.A.J. Pyruvate kinase M2 regulates Hif-1α activity and IL-1β induction and is a critical determinant of the warburg effect in LPS-activated macrophages. Cell Metab. 2015 21 1 65 80 10.1016/j.cmet.2014.12.005 25565206
    [Google Scholar]
  88. Tannahill G.M. Curtis A.M. Adamik J. McDermott P.E.M. McGettrick A.F. Goel G. Frezza C. Bernard N.J. Kelly B. Foley N.H. Zheng L. Gardet A. Tong Z. Jany S.S. Corr S.C. Haneklaus M. Caffrey B.E. Pierce K. Walmsley S. Beasley F.C. Cummins E. Nizet V. Whyte M. Taylor C.T. Lin H. Masters S.L. Gottlieb E. Kelly V.P. Clish C. Auron P.E. Xavier R.J. O’Neill L.A.J. Succinate is an inflammatory signal that induces IL-1β through HIF-1α. Nature 2013 496 7444 238 242 10.1038/nature11986 23535595
    [Google Scholar]
  89. Yang H. Zhong J.T. Zhou S.H. Han H.M. Roles of GLUT-1 and HK-II expression in the biological behavior of head and neck cancer. Oncotarget 2019 10 32 3066 3083 10.18632/oncotarget.24684 31105886
    [Google Scholar]
  90. Fukuzumi M. Shinomiya H. Shimizu Y. Ohishi K. Utsumi S. Endotoxin-induced enhancement of glucose influx into murine peritoneal macrophages via GLUT-1. Infect. Immun. 1996 64 1 108 112 10.1128/iai.64.1.108‑112.1996 8557327
    [Google Scholar]
  91. Wolf A.J. Reyes C.N. Liang W. Becker C. Shimada K. Wheeler M.L. Cho H.C. Popescu N.I. Coggeshall K.M. Arditi M. Underhill D.M. Hexokinase is an innate immune receptor for the detection of bacterial peptidoglycan. Cell 2016 166 3 624 636 10.1016/j.cell.2016.05.076 27374331
    [Google Scholar]
  92. Silva D.W.S. Puyou G.A. Puyou G.M.T. Sanchez M.R. De Felice F.G. de Meis L. Oliveira M.F. Galina A. Mitochondrial bound hexokinase activity as a preventive antioxidant defense: Steady-state ADP formation as a regulatory mechanism of membrane potential and reactive oxygen species generation in mitochondria. J. Biol. Chem. 2004 279 38 39846 39855 10.1074/jbc.M403835200 15247300
    [Google Scholar]
  93. Pastorino J.G. Shulga N. Hoek J.B. Mitochondrial binding of hexokinase II inhibits Bax-induced cytochrome c release and apoptosis. J. Biol. Chem. 2002 277 9 7610 7618 10.1074/jbc.M109950200 11751859
    [Google Scholar]
  94. Finucane O.M. Sugrue J. Araiz R.A. Sestier G.M.V. Lynch M.A. The NLRP3 inflammasome modulates glycolysis by increasing PFKFB3 in an IL-1β-dependent manner in macrophages. Sci. Rep. 2019 9 1 4034 10.1038/s41598‑019‑40619‑1 30858427
    [Google Scholar]
  95. Ménégaut L. Thomas C. Lagrost L. Masson D. Fatty acid metabolism in macrophages: A target in cardio-metabolic diseases. Curr. Opin. Lipidol. 2017 28 1 19 26 10.1097/MOL.0000000000000370 27870652
    [Google Scholar]
  96. Karasawa T. Takahashi M. The crystal-induced activation of NLRP3 inflammasomes in atherosclerosis. Inflamm. Regen. 2017 37 1 18 10.1186/s41232‑017‑0050‑9 29259717
    [Google Scholar]
  97. Rajamäki K. Lappalainen J. Öörni K. Välimäki E. Matikainen S. Kovanen P.T. Eklund K.K. Cholesterol crystals activate the NLRP3 inflammasome in human macrophages: A novel link between cholesterol metabolism and inflammation. PLoS One 2010 5 7 e11765 10.1371/journal.pone.0011765 20668705
    [Google Scholar]
  98. Sanman L.E. Qian Y. Eisele N.A. Ng T.M. van der Linden W.A. Monack D.M. Weerapana E. Bogyo M. Disruption of glycolytic flux is a signal for inflammasome signaling and pyroptotic cell death. eLife 2016 5 e13663 10.7554/eLife.13663 27011353
    [Google Scholar]
  99. Tan V.P. Miyamoto S. HK2/hexokinase-II integrates glycolysis and autophagy to confer cellular protection. Autophagy 2015 11 6 963 964 10.1080/15548627.2015.1042195 26075878
    [Google Scholar]
  100. Blaha C.S. Ramakrishnan G. Jeon S.M. Nogueira V. Rho H. Kang S. Bhaskar P. Terry A.R. Aissa A.F. Frolov M.V. Patra K.C. Robey B.R. Hay N. A non-catalytic scaffolding activity of hexokinase 2 contributes to EMT and metastasis. Nat. Commun. 2022 13 1 899 10.1038/s41467‑022‑28440‑3 35173161
    [Google Scholar]
  101. Bao H. Wang C. Jin Y. Meng Q. Wu J. Liu Q. Sun H. The contributory role of GSK3β in hypertension exacerbating atherosclerosis by regulating the OMA1/ PGC1α pathway. Apoptosis 2024 1 14 10.1007/s10495‑024‑02029‑1 39427090
    [Google Scholar]
  102. Patel S. Werstuck G.H. Macrophage function and the role of GSK3. Int. J. Mol. Sci. 2021 22 4 2206 10.3390/ijms22042206 33672232
    [Google Scholar]
  103. Ros S. Schulze A. Balancing glycolytic flux: The role of 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatases in cancer metabolism. Cancer Metab. 2013 1 1 8 10.1186/2049‑3002‑1‑8 24280138
    [Google Scholar]
  104. Prados R.J.C. Través P.G. Cuenca J. Rico D. Aragonés J. Sanz M.P. Cascante M. Boscá L. Substrate fate in activated macrophages: A comparison between innate, classic, and alternative activation. J. Immunol. 2010 185 1 605 614 10.4049/jimmunol.0901698 20498354
    [Google Scholar]
  105. Jiang H. Shi H. Sun M. Wang Y. Meng Q. Guo P. Cao Y. Chen J. Gao X. Li E. Liu J. PFKFB3-Driven macrophage glycolytic metabolism is a crucial component of innate antiviral defense. J. Immunol. 2016 197 7 2880 2890 10.4049/jimmunol.1600474 27566823
    [Google Scholar]
  106. Guo S. Li A. Fu X. Li Z. Cao K. Song M. Huang S. Li Z. Yan J. Wang L. Dai X. Feng D. Wang Y. He J. Huo Y. Xu Y. Gene-dosage effect of PFKFB3 on monocyte/macrophage biology in atherosclerosis. Br. J. Pharmacol. 2022 179 21 4974 4991 10.1111/bph.15926 35834356
    [Google Scholar]
  107. Poels K. Schnitzler J.G. Waissi F. Levels J.H.M. Stroes E.S.G. Daemen M.J.A.P. Lutgens E. Pennekamp A.M. De Kleijn D.P.V. Seijkens T.T.P. Kroon J. Inhibition of PFKFB3 hampers the progression of atherosclerosis and promotes plaque stability. Front. Cell Dev. Biol. 2020 8 581641 10.3389/fcell.2020.581641 33282864
    [Google Scholar]
  108. Perrotta P. Van der Veken B. Van Der Veken P. Pintelon I. Roosens L. Adriaenssens E. Timmerman V. Guns P.J. De Meyer G.R.Y. Martinet W. Partial inhibition of glycolysis reduces atherogenesis independent of intraplaque neovascularization in mice. Arterioscler. Thromb. Vasc. Biol. 2020 40 5 1168 1181 10.1161/ATVBAHA.119.313692 32188275
    [Google Scholar]
  109. Zhou L. Li J. Wang J. Niu X. Li J. Zhang K. Pathogenic role of PFKFB3 in endothelial inflammatory diseases. Front. Mol. Biosci. 2024 11 1454456 10.3389/fmolb.2024.1454456 39318551
    [Google Scholar]
  110. De Bock K. Georgiadou M. Schoors S. Kuchnio A. Wong B.W. Cantelmo A.R. Quaegebeur A. Ghesquière B. Cauwenberghs S. Eelen G. Phng L.K. Betz I. Tembuyser B. Brepoels K. Welti J. Geudens I. Segura I. Cruys B. Bifari F. Decimo I. Blanco R. Wyns S. Vangindertael J. Rocha S. Collins R.T. Munck S. Daelemans D. Imamura H. Devlieger R. Rider M. Veldhoven V.P.P. Schuit F. Bartrons R. Hofkens J. Fraisl P. Telang S. DeBerardinis R.J. Schoonjans L. Vinckier S. Chesney J. Gerhardt H. Dewerchin M. Carmeliet P. Role of PFKFB3-driven glycolysis in vessel sprouting. Cell 2013 154 3 651 663 10.1016/j.cell.2013.06.037 23911327
    [Google Scholar]
  111. Jaiyesimi O. Kuppuswamy S. Zhang G. Batan S. Zhi W. Ganta V.C. Glycolytic PFKFB3 and glycogenic UGP2 axis regulates perfusion recovery in experimental hind limb ischemia. Arterioscler. Thromb. Vasc. Biol. 2024 44 8 1764 1783 10.1161/ATVBAHA.124.320665 38934117
    [Google Scholar]
  112. Qin W. Qin K. Zhang Y. Jia W. Chen Y. Cheng B. Peng L. Chen N. Liu Y. Zhou W. Wang Y.L. Chen X. Wang C. S-glycosylation-based cysteine profiling reveals regulation of glycolysis by itaconate. Nat. Chem. Biol. 2019 15 10 983 991 10.1038/s41589‑019‑0323‑5 31332308
    [Google Scholar]
  113. Millet P. Vachharajani V. McPhail L. Yoza B. McCall C.E. GAPDH binding to TNF-α mRNA contributes to posttranscriptional repression in monocytes: A novel mechanism of communication between inflammation and metabolism. J. Immunol. 2016 196 6 2541 2551 10.4049/jimmunol.1501345 26843329
    [Google Scholar]
  114. Pirela R.M. Alviárez A.D. Rojas V. Kemmerling U. Cáceres A.J. Michels P.A. Concepción J.L. Quiñones W. Phosphoglycerate kinase: Structural aspects and functions, with special emphasis on the enzyme from Kinetoplastea. Open Biol. 2020 10 11 200302 10.1098/rsob.200302 33234025
    [Google Scholar]
  115. Yagi H. Kasai T. Rioual E. Ikeya T. Kigawa T. Molecular mechanism of glycolytic flux control intrinsic to human phosphoglycerate kinase. Proc. Natl. Acad. Sci. 2021 118 50 e2112986118 10.1073/pnas.2112986118 34893542
    [Google Scholar]
  116. Kokotos A.C. Antoniazzi A.M. Unda S.R. Ko M.S. Park D. Eliezer D. Kaplitt M.G. De Camilli P. Ryan T.A. Phosphoglycerate kinase is a central leverage point in Parkinson’s disease–driven neuronal metabolic deficits. Sci. Adv. 2024 10 34 eadn6016 10.1126/sciadv.adn6016 39167658
    [Google Scholar]
  117. Li X. Jiang Y. Meisenhelder J. Yang W. Hawke D.H. Zheng Y. Xia Y. Aldape K. He J. Hunter T. Wang L. Lu Z. Mitochondria-translocated PGK1 functions as a protein kinase to coordinate glycolysis and the TCA cycle in tumorigenesis. Mol. Cell 2016 61 5 705 719 10.1016/j.molcel.2016.02.009 26942675
    [Google Scholar]
  118. Guo Z. Zhang Y. Wang H. Liao L. Ma L. Zhao Y. Yang R. Li X. Niu J. Chu Q. Fu Y. Li B. Yang C. Hypoxia-induced downregulation of PGK1 crotonylation promotes tumorigenesis by coordinating glycolysis and the TCA cycle. Nat. Commun. 2024 15 1 6915 10.1038/s41467‑024‑51232‑w 39134530
    [Google Scholar]
  119. Hanssen N.M.J. Stehouwer C.D.A. Schalkwijk C.G. Methylglyoxal and glyoxalase I in atherosclerosis. Biochem. Soc. Trans. 2014 42 2 443 449 10.1042/BST20140001 24646258
    [Google Scholar]
  120. Lai S.W.T. Gonzalez L.E.D.J. Zoukari T. Ki P. Shuck S.C. Methylglyoxal and its adducts: Induction, repair, and association with disease. Chem. Res. Toxicol. 2022 35 10 1720 1746 10.1021/acs.chemrestox.2c00160 36197742
    [Google Scholar]
  121. Prantner D. Nallar S. Richard K. Spiegel D. Collins K.D. Vogel S.N. Classically activated mouse macrophages produce methylglyoxal that induces a TLR4- and RAGE-independent proinflammatory response. J. Leukoc. Biol. 2021 109 3 605 619 10.1002/JLB.3A0520‑745RR 32678947
    [Google Scholar]
  122. Stanton C. Buasakdi C. Sun J. Levitan I. Bora P. Kutseikin S. Wiseman R.L. Bollong M.J. The glycolytic metabolite methylglyoxal covalently inactivates the NLRP3 inflammasome. Cell Rep. 2024 43 9 114688 10.1016/j.celrep.2024.114688 39196782
    [Google Scholar]
  123. Bollong M.J. Lee G. Coukos J.S. Yun H. Zambaldo C. Chang J.W. Chin E.N. Ahmad I. Chatterjee A.K. Lairson L.L. Schultz P.G. Moellering R.E. A metabolite-derived protein modification integrates glycolysis with KEAP1–NRF2 signalling. Nature 2018 562 7728 600 604 10.1038/s41586‑018‑0622‑0 30323285
    [Google Scholar]
  124. Su Y. Qadri S.M. Wu L. Liu L. Methylglyoxal modulates endothelial nitric oxide synthase-associated functions in EA.hy926 endothelial cells. Cardiovasc. Diabetol. 2013 12 1 134 10.1186/1475‑2840‑12‑134 24050620
    [Google Scholar]
  125. Su Y. Qadri S.M. Hossain M. Wu L. Liu L. Uncoupling of eNOS contributes to redox-sensitive leukocyte recruitment and microvascular leakage elicited by methylglyoxal. Biochem. Pharmacol. 2013 86 12 1762 1774 10.1016/j.bcp.2013.10.008 24144633
    [Google Scholar]
  126. Dhar I. Dhar A. Wu L. Desai K. Arginine attenuates methylglyoxal- and high glucose-induced endothelial dysfunction and oxidative stress by an endothelial nitric-oxide synthase-independent mechanism. J. Pharmacol. Exp. Ther. 2012 342 1 196 204 10.1124/jpet.112.192112 22518022
    [Google Scholar]
  127. Wang J. Yang P. Yu T. Gao M. Liu D. Zhang J. Lu C. Chen X. Zhang X. Liu Y. Lactylation of PKM2 suppresses inflammatory metabolic adaptation in pro-inflammatory macrophages. Int. J. Biol. Sci. 2022 18 16 6210 6225 10.7150/ijbs.75434 36439872
    [Google Scholar]
  128. Alquraishi M. Puckett D.L. Alani D.S. Humidat A.S. Frankel V.D. Donohoe D.R. Whelan J. Bettaieb A. Pyruvate kinase M2: A simple molecule with complex functions. Free Radic. Biol. Med. 2019 143 176 192 10.1016/j.freeradbiomed.2019.08.007 31401304
    [Google Scholar]
  129. Takenaka M. Noguchi T. Sadahiro S. Hirai H. Yamada K. Matsuda T. Imai E. Tanaka T. Isolation and characterization of the human pyruvate kinase M gene. Eur. J. Biochem. 1991 198 1 101 106 10.1111/j.1432‑1033.1991.tb15991.x 2040271
    [Google Scholar]
  130. Yang W. Lu Z. Regulation and function of pyruvate kinase M2 in cancer. Cancer Lett. 2013 339 2 153 158 10.1016/j.canlet.2013.06.008 23791887
    [Google Scholar]
  131. Kawahisa T.J.E. Hiroki C.H. Silva C.M.S. Nascimento D.C. Públio G.A. Martins T.V. Damasceno L.E.A. Veras F.P. Viacava P.R. Sukesada F.Y. Day E.A. Zotta A. Ryan T.A.J. da Silva M.R. Cunha T.M. Lopes N.P. Cunha F.Q. O’Neill L.A.J. Filho A.J.C. The metabolic function of pyruvate kinase M2 regulates reactive oxygen species production and microbial killing by neutrophils. Nat. Commun. 2023 14 1 4280 10.1038/s41467‑023‑40021‑6 37460614
    [Google Scholar]
  132. Bekkering S. van den Munckhof I. Nielen T. Lamfers E. Dinarello C. Rutten J. de Graaf J. Joosten L.A.B. Netea M.G. Gomes M.E.R. Riksen N.P. Innate immune cell activation and epigenetic remodeling in symptomatic and asymptomatic atherosclerosis in humans in vivo. Atherosclerosis 2016 254 228 236 10.1016/j.atherosclerosis.2016.10.019 27764724
    [Google Scholar]
  133. Shirai T. Nazarewicz R.R. Wallis B.B. Yanes R.E. Watanabe R. Hilhorst M. Tian L. Harrison D.G. Giacomini J.C. Assimes T.L. Goronzy J.J. Weyand C.M. The glycolytic enzyme PKM2 bridges metabolic and inflammatory dysfunction in coronary artery disease. J. Exp. Med. 2016 213 3 337 354 10.1084/jem.20150900 26926996
    [Google Scholar]
  134. Li Z.L. Ding L. Ma R.X. Zhang Y. Zhang Y.L. Ni W.J. Tang T.T. Wang G.H. Wang B. Lv L.L. Wu Q.L. Wen Y. Liu B.C. Activation of HIF-1α C-terminal transactivation domain protects against hypoxia-induced kidney injury through hexokinase 2-mediated mitophagy. Cell Death Dis. 2023 14 5 339 10.1038/s41419‑023‑05854‑5 37225700
    [Google Scholar]
  135. Shen N. Wang Y. Sun X. Bai X. He J. Cui Q. Qian J. Zhu H. Chen Y. Xing R. Liu Q. Wu Y. Li J. Lai W. Sun S. Ji N. Liu Y. Expression of hypoxia-inducible factor 1α, glucose transporter 1, and hexokinase 2 in primary central nervous system lymphoma and the correlation with the biological behaviors. Brain Behav. 2020 10 8 e01718 10.1002/brb3.1718 32533646
    [Google Scholar]
  136. Corcoran S.E. O’Neill L.A.J. HIF-1α and metabolic reprogramming in inflammation. J. Clin. Invest. 2016 126 10 3699 3707 10.1172/JCI84431 27571407
    [Google Scholar]
  137. Sun X. Huang Q. Peng F. Wang J. Zhao W. Guo G. Expression and clinical significance of HKII and HIF-1α in grade groups of prostate cancer. Front. Genet. 2021 12 680928 10.3389/fgene.2021.680928 34220956
    [Google Scholar]
  138. Lee S.J. Quach T.C.H. Jung K.H. Paik J.Y. Lee J.H. Park J.W. Lee K.H. Oxidized low-density lipoprotein stimulates macrophage 18F-FDG uptake via hypoxia-inducible factor-1α activation through Nox2-dependent reactive oxygen species generation. J. Nucl. Med. 2014 55 10 1699 1705 10.2967/jnumed.114.139428 25214643
    [Google Scholar]
  139. Luo W. Hu H. Chang R. Zhong J. Knabel M. O’Meally R. Cole R.N. Pandey A. Semenza G.L. Pyruvate kinase M2 is a PHD3-stimulated coactivator for hypoxia-inducible factor 1. Cell 2011 145 5 732 744 10.1016/j.cell.2011.03.054 21620138
    [Google Scholar]
  140. Yang W. Xia Y. Ji H. Zheng Y. Liang J. Huang W. Gao X. Aldape K. Lu Z. Nuclear PKM2 regulates β- catenin transactivation upon EGFR activation. Nature 2011 480 7375 118 122 10.1038/nature10598 22056988
    [Google Scholar]
  141. Jemal M. Getinet M. Amare G.A. Tegegne B.A. Baylie T. Mengistu E.F. Osman E.E. Waritu C.N. Adugna A. Non-metabolic enzyme function of pyruvate kinase M2 in breast cancer. Front. Oncol. 2024 14 1450325 10.3389/fonc.2024.1450325 39411137
    [Google Scholar]
  142. Zhang S. Liao Z. Li S. Luo Y. Non-metabolic enzyme function of PKM2 in hepatocellular carcinoma: A review. Medicine 2023 102 42 e35571 10.1097/MD.0000000000035571 37861491
    [Google Scholar]
  143. Slater S.C. Koutsouki E. Jackson C.L. Bush R.C. Angelini G.D. Newby A.C. George S.J. R-cadherin:beta- catenin complex and its association with vascular smooth muscle cell proliferation. Arterioscler. Thromb. Vasc. Biol. 2004 24 7 1204 1210 10.1161/01.ATV.0000130464.24599.e0 15117735
    [Google Scholar]
  144. Wang X. Xiao Y. Mou Y. Zhao Y. Blankesteijn W.M. Hall J.L. A role for the beta- catenin/T-cell factor signaling cascade in vascular remodeling. Circ. Res. 2002 90 3 340 347 10.1161/hh0302.104466 11861424
    [Google Scholar]
  145. Bedel A. Salvayre N.A. Heeneman S. Grazide M.H. Thiers J.C. Salvayre R. Schwalm M.F. E-cadherin/beta-catenin/T-cell factor pathway is involved in smooth muscle cell proliferation elicited by oxidized low-density lipoprotein. Circ. Res. 2008 103 7 694 701 10.1161/CIRCRESAHA.107.166405 18703780
    [Google Scholar]
  146. Paula O.G.H. Liu S. Maira A. Ressa G. Ferreira G.C. Quintar A. Jayakumar S. Almonte V. Parikh D. Valenta T. Basler K. Hla T. Bernal R.D.F. Sibinga N.E.S. The β-catenin C terminus links Wnt and sphingosine-1-phosphate signaling pathways to promote vascular remodeling and atherosclerosis. Sci. Adv. 2024 10 11 eadg9278 10.1126/sciadv.adg9278 38478616
    [Google Scholar]
  147. Chen Q. Lv J. Yang W. Xu B. Wang Z. Yu Z. Wu J. Yang Y. Han Y. Targeted inhibition of STAT3 as a potential treatment strategy for atherosclerosis. Theranostics 2019 9 22 6424 6442 10.7150/thno.35528 31588227
    [Google Scholar]
  148. Mimura J. Itoh K. Role of NRF2 in the pathogenesis of atherosclerosis. Free Radic. Biol. Med. 2015 88 Pt B 221 232 10.1016/j.freeradbiomed.2015.06.019 26117321
    [Google Scholar]
  149. Mills E.L. Ryan D.G. Prag H.A. Dikovskaya D. Menon D. Zaslona Z. Jedrychowski M.P. Costa A.S.H. Higgins M. Hams E. Szpyt J. Runtsch M.C. King M.S. McGouran J.F. Fischer R. Kessler B.M. McGettrick A.F. Hughes M.M. Carroll R.G. Booty L.M. Knatko E.V. Meakin P.J. Ashford M.L.J. Modis L.K. Brunori G. Sévin D.C. Fallon P.G. Caldwell S.T. Kunji E.R.S. Chouchani E.T. Frezza C. Kostova D.A.T. Hartley R.C. Murphy M.P. O’Neill L.A. Itaconate is an anti-inflammatory metabolite that activates NRF2 via alkylation of KEAP1. Nature 2018 556 7699 113 117 10.1038/nature25986 29590092
    [Google Scholar]
  150. Song J. Zhang Y. Frieler R.A. Andren A. Wood S. Tyrrell D.J. Sajjakulnukit P. Deng J.C. Lyssiotis C.A. Mortensen R.M. Salmon M. Goldstein D.R. Itaconate suppresses atherosclerosis by activating a NRF2-dependent antiinflammatory response in macrophages in mice. J. Clin. Invest. 2023 134 3 e173034 10.1172/JCI173034 38085578
    [Google Scholar]
  151. Freigang S. Ampenberger F. Spohn G. Heer S. Shamshiev A.T. Kisielow J. Hersberger M. Yamamoto M. Bachmann M.F. Kopf M. NRF2 is essential for cholesterol crystal-induced inflammasome activation and exacerbation of atherosclerosis. Eur. J. Immunol. 2011 41 7 2040 2051 10.1002/eji.201041316 21484785
    [Google Scholar]
  152. Harada N. Ito K. Hosoya T. Mimura J. Maruyama A. Noguchi N. Yagami K. Morito N. Takahashi S. Maher J.M. Yamamoto M. Itoh K. NRF2 in bone marrow-derived cells positively contributes to the advanced stage of atherosclerotic plaque formation. Free Radic. Biol. Med. 2012 53 12 2256 2262 10.1016/j.freeradbiomed.2012.10.001 23051009
    [Google Scholar]
  153. Siragusa M. Thöle J. Bibli S.I. Luck B. Loot A.E. de Silva K. Wittig I. Heidler J. Stingl H. Randriamboavonjy V. Kohlstedt K. Brüne B. Weigert A. Fisslthaler B. Fleming I. Nitric oxide maintains endothelial redox homeostasis through PKM2 inhibition. EMBO J. 2019 38 17 e100938 10.15252/embj.2018100938 31328803
    [Google Scholar]
  154. Ye L. Jiang Y. Zhang M. Crosstalk between glucose metabolism, lactate production and immune response modulation. Cytokine Growth Factor Rev. 2022 68 81 92 10.1016/j.cytogfr.2022.11.001 36376165
    [Google Scholar]
  155. Sun Z. Han Y. Song S. Chen T. Han Y. Liu Y. Activation of GPR81 by lactate inhibits oscillatory shear stress-induced endothelial inflammation by activating the expression of KLF2. IUBMB Life 2019 71 12 2010 2019 10.1002/iub.2151 31444899
    [Google Scholar]
  156. Fang Y. Li Z. Yang L. Li W. Wang Y. Kong Z. Miao J. Chen Y. Bian Y. Zeng L. Emerging roles of lactate in acute and chronic inflammation. Cell Commun. Signal. 2024 22 1 276 10.1186/s12964‑024‑01624‑8 38755659
    [Google Scholar]
  157. Zhang D. Tang Z. Huang H. Zhou G. Cui C. Weng Y. Liu W. Kim S. Lee S. Neut P.M. Ding J. Czyz D. Hu R. Ye Z. He M. Zheng Y.G. Shuman H.A. Dai L. Ren B. Roeder R.G. Becker L. Zhao Y. Metabolic regulation of gene expression by histone lactylation. Nature 2019 574 7779 575 580 10.1038/s41586‑019‑1678‑1 31645732
    [Google Scholar]
  158. Jiang R. Ren W.J. Wang L.Y. Zhang W. Jiang Z.H. Zhu G.Y. Targeting lactate: An emerging strategy for macrophage regulation in chronic inflammation and cancer. Biomolecules 2024 14 10 1202 10.3390/biom14101202 39456135
    [Google Scholar]
  159. Williams N.C. O’Neill L.A.J. A role for the krebs cycle intermediate citrate in metabolic reprogramming in innate immunity and inflammation. Front. Immunol. 2018 9 141 10.3389/fimmu.2018.00141 29459863
    [Google Scholar]
  160. Ryan D.G. O’Neill L.A.J. Krebs cycle reborn in macrophage immunometabolism. Annu. Rev. Immunol. 2020 38 1 289 313 10.1146/annurev‑immunol‑081619‑104850 31986069
    [Google Scholar]
  161. Liang Y. Chen Y. Li L. Zhang S. Xiao J. Wei D. Krebs cycle rewired: Driver of atherosclerosis progression? Curr. Med. Chem. 2022 29 13 2322 2333 10.2174/0929867328666210806105246 34365937
    [Google Scholar]
  162. Iacobazzi V Infantino V. Citrate – new functions for an old metabolite. Biol. Chem. 2014 395 4 387 399 10.1515/hsz‑2013‑0271
    [Google Scholar]
  163. Infantino V. Convertini P. Cucci L. Panaro M.A. Di Noia M.A. Calvello R. Palmieri F. Iacobazzi V. The mitochondrial citrate carrier: A new player in inflammation. Biochem. J. 2011 438 3 433 436 10.1042/BJ20111275 21787310
    [Google Scholar]
  164. Xu J. Zheng Y. Zhao Y. Zhang Y. Li H. Zhang A. Wang X. Wang W. Hou Y. Wang J. Succinate/IL-1β signaling axis promotes the inflammatory progression of endothelial and exacerbates atherosclerosis. Front. Immunol. 2022 13 817572 10.3389/fimmu.2022.817572
    [Google Scholar]
  165. Wen H. Ting J.P.Y. Agitation by suffocation: How hypoxia activates innate immunity via the Warburg effect. Cell Metab. 2013 17 6 814 815 10.1016/j.cmet.2013.05.016 23747241
    [Google Scholar]
  166. Viola A. Munari F. Rodríguez S.R. Scolaro T. Castegna A. The metabolic signature of macrophage responses. Front. Immunol. 2019 10 1462 10.3389/fimmu.2019.01462 31333642
    [Google Scholar]
  167. Wang F. Wang K. Xu W. Zhao S. Ye D. Wang Y. Xu Y. Zhou L. Chu Y. Zhang C. Qin X. Yang P. Yu H. SIRT5 desuccinylates and activates pyruvate kinase M2 to block macrophage IL-1β production and to prevent DSS-induced colitis in mice. Cell Rep. 2017 19 11 2331 2344 10.1016/j.celrep.2017.05.065 28614718
    [Google Scholar]
  168. Li Z. Zheng W. Kong W. Zeng T. Itaconate: A potent macrophage immunomodulator. Inflammation 2023 46 4 1177 1191 10.1007/s10753‑023‑01819‑0 37142886
    [Google Scholar]
  169. Li Y. Gong W. Li W. Liu P. Liu J. Jiang H. Zheng T. Wu J. Wu X. Zhao Y. Ren J. The Irg-1-Itaconate axis: A regulatory hub for immunity and metabolism in macrophages. Int. Rev. Immunol. 2023 42 5 364 378 10.1080/08830185.2022.2067153 35468044
    [Google Scholar]
  170. Ni L. Xiao J. Zhang D. Shao Z. Huang C. Wang S. Wu Y. Tian N. Sun L. Wu A. Zhou Y. Wang X. Zhang X. Immune-responsive gene 1/itaconate activates nuclear factor erythroid 2-related factor 2 in microglia to protect against spinal cord injury in mice. Cell Death Dis. 2022 13 2 140 10.1038/s41419‑022‑04592‑4 35145070
    [Google Scholar]
  171. Palmieri E.M. McGinity C. Wink D.A. McVicar D.W. Nitric oxide in macrophage immunometabolism: Hiding in plain sight. Metabolites 2020 10 11 429 10.3390/metabo10110429 33114647
    [Google Scholar]
  172. Thwe P.M. Amiel E. The role of nitric oxide in metabolic regulation of Dendritic cell immune function. Cancer Lett. 2018 412 236 242 10.1016/j.canlet.2017.10.032 29107106
    [Google Scholar]
  173. Palmieri E.M. Cotto G.M. Baseler W.A. Davies L.C. Ghesquière B. Maio N. Rice C.M. Rouault T.A. Cassel T. Higashi R.M. Lane A.N. Fan T.W.M. Wink D.A. McVicar D.W. Nitric oxide orchestrates metabolic rewiring in M1 macrophages by targeting aconitase 2 and pyruvate dehydrogenase. Nat. Commun. 2020 11 1 698 10.1038/s41467‑020‑14433‑7 32019928
    [Google Scholar]
  174. Khan M.H. Rochlani Y. Yandrapalli S. Aronow W.S. Frishman W.H. Vulnerable plaque. Cardiol. Rev. 2020 28 1 3 9 10.1097/CRD.0000000000000238 30489331
    [Google Scholar]
  175. Meng T. He D. Han Z. Shi R. Wang Y. Ren B. Zhang C. Mao Z. Luo G. Deng J. Nanomaterial-based repurposing of macrophage metabolism and its applications. Nano-Micro Lett. 2024 16 1 246 10.1007/s40820‑024‑01455‑9 39007981
    [Google Scholar]
  176. Wang Y. Zhang Y. Wang Z. Zhang J. Qiao R.R. Xu M. Yang N. Gao L. Qiao H. Gao M. Cao F. Optical/MRI dual-modality imaging of M1 macrophage polarization in atherosclerotic plaque with MARCO-targeted upconversion luminescence probe. Biomaterials 2019 219 119378 10.1016/j.biomaterials.2019.119378 31382209
    [Google Scholar]
  177. Kou H. Yang H. Molecular imaging nanoprobes and their applications in atherosclerosis diagnosis. Theranostics 2024 14 12 4747 4772 10.7150/thno.96037 39239513
    [Google Scholar]
  178. Jeong H.J. Yoo R.J. Kim J.K. Kim M.H. Park S.H. Kim H. Lim J.W. Do S.H. Lee K.C. Lee Y.J. Kim D.W. Macrophage cell tracking PET imaging using mesoporous silica nanoparticles via in vivo bioorthogonal F-18 labeling. Biomaterials 2019 199 32 39 10.1016/j.biomaterials.2019.01.043 30735894
    [Google Scholar]
  179. Kojima H. Urano Y. Kikuchi K. Higuchi T. Hirata Y. Nagano T. Fluorescent indicators for imaging nitric oxide production. Angew. Chem. Int. Ed. 1999 38 21 3209 3212 10.1002/(SICI)1521‑3773(19991102)38:21<3209::AID‑ANIE3209>3.0.CO;2‑6 10556905
    [Google Scholar]
  180. Mao Z. Ye M. Hu W. Ye X. Wang Y. Zhang H. Li C. Liu Z. Design of a ratiometric two-photon probe for imaging of hypochlorous acid (HClO) in wounded tissues. Chem. Sci. 2018 9 28 6035 6040 10.1039/C8SC01697F 30079216
    [Google Scholar]
  181. Ramesh A. Kumar S. Brouillard A. Nandi D. Kulkarni A. A nitric oxide (NO) nanoreporter for noninvasive real-time imaging of macrophage immunotherapy. Adv. Mater. 2020 32 24 2000648 10.1002/adma.202000648 32390270
    [Google Scholar]
  182. Sasaki E. Kojima H. Nishimatsu H. Urano Y. Kikuchi K. Hirata Y. Nagano T. Highly sensitive near-infrared fluorescent probes for nitric oxide and their application to isolated organs. J. Am. Chem. Soc. 2005 127 11 3684 3685 10.1021/ja042967z 15771488
    [Google Scholar]
  183. Yu H. Ren P. Pan X. Zhang X. Ma J. Chen J. Sheng J. Luo H. Lu H. Chen G. Intracellular delivery of itaconate by metal–organic framework-anchored hydrogel microspheres for osteoarthritis therapy. Pharmaceutics 2023 15 3 724 10.3390/pharmaceutics15030724 36986584
    [Google Scholar]
  184. Li L. Mou J. Han Y. Wang M. Lu S. Ma Q. Wang J. Ye J. Sun G. Calenduloside e modulates macrophage polarization via KLF2-regulated glycolysis, contributing to attenuates atherosclerosis. Int. Immunopharmacol. 2023 117 109730 10.1016/j.intimp.2023.109730 36878047
    [Google Scholar]
/content/journals/cmc/10.2174/0109298673339364241224102645
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Role of Glycolysis and Nitric Oxide Pathway Crosstalk in Macrophages in Atherosclerosis
Bentham Science Publishers ; https://doi.org/10.2174/0109298673339364241224102645
/content/journals/cmc/10.2174/0109298673339364241224102645
/content/journals/cmc/10.2174/0109298673339364241224102645
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  • Article Type:     Review Article
Keywords: Atherosclerosis ; immunometabolism ; macrophages ; innate immune system ; glycolysis ; nitric oxide

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