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- Volume 22, Issue 5, 2024
Current Vascular Pharmacology - Volume 22, Issue 5, 2024
Volume 22, Issue 5, 2024
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Cellular and Molecular Mechanisms of Neuronal Degeneration in Early-Stage Diabetic Retinopathy
Authors: Andrew Callan, Sonal Jha, Laura Valdez and Andrew TsinBackground: Studies on the early retinal changes in Diabetic Retinopathy (DR) have demonstrated that neurodegeneration precedes vascular abnormalities like microaneurysms or intraretinal hemorrhages. Therefore, there is a growing field of study to analyze the cellular and molecular pathways involved to allow for the development of novel therapeutics to prevent the onset or delay the progression of DR. Molecular Mechanisms: Oxidative stress and mitochondrial dysfunction contribute to neurodegeneration through pathways involving polyol, hexosamine, advanced glycation end products, and protein kinase C. Potential interventions targeting these pathways include aldose reductase inhibitors and protein kinase C inhibitors. Neurotrophic factor imbalances, notably brain-derived neurotrophic factor and nerve growth factor, also play a role in early neurodegeneration, and supplementation of these neurotrophic factors show promise in mitigating neurodegeneration. Cellular Mechanisms: Major cellular mechanisms of neurodegeneration include caspase-mediated apoptosis, glial cell reactivity, and glutamate excitotoxicity. Therefore, inhibitors of these pathways are potential therapeutic avenues. Vascular Component: The nitric oxide pathway, critical for neurovascular coupling, is disrupted in DR due to increased reactive oxygen species. Vascular Endothelial Growth Factor (VEGF), a long-known angiogenic factor, has demonstrated both damaging and neuroprotective effects, prompting a careful consideration of long-term anti-VEGF therapy. Conclusion: Current DR treatments primarily address vascular symptoms but fall short of preventing or halting the disease. Insights into the mechanisms of retinal neurodegeneration in the setting of diabetes mellitus not only enhance our understanding of DR but also pave the way for future therapeutic interventions aimed at preventing disease progression and preserving vision.
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Cardioprotective Effects of Exercise: The Role of Irisin and Exosome
Authors: Yuehuan Wang, Yi Yang and Yanjuan SongExercise is an effective measure for preventing and treating cardiovascular diseases, although the exact molecular mechanism remains unknown. Previous studies have shown that both irisin and exosomes can improve the course of cardiovascular disease independently. Therefore, it is speculated that the cardiovascular protective effect of exercise is also related to its ability to regulate the concentrations of irisin and exosomes in the circulatory system. In this review, the potential synergistic interactions between irisin and exosomes are examined, as well as the underlying mechanisms including the AMPK/PI3K/AKT pathway, the TGFβ1/Smad2/3 pathway, the PI3K/AKT/VEGF pathway, and the PTEN/PINK1/Parkin pathway are examined. This paper provides evidence to propose that exercise promotes the release of exosomes enriched with irisin, miR-486-5p and miR-342-5p from skeletal muscles, which results in the activation protective networks in the cardiovascular system. Moreover, the potential synergistic effect in exosomal cargo can provide new ideas for clinical research of exercise mimics.
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Antiplatelet Effect of Low-Dose Prasugrel in Elderly Patients Undergoing Percutaneous Coronary Interventions
Authors: Monica Verdoia, Matteo Nardin, Rocco Gioscia, Andrea Rognoni and Giuseppe De LucaBackground: Low-dose prasugrel (5 mg) has been proposed for patients with Acute Coronary Syndrome (ACS) and advanced age or low body weight. However, the routine use of dose-adjusted prasugrel in this high-risk subset of patients is still debated. Aim: This study aimed to assess the prevalence and predictors of HRPR among elderly patients treated with low-dose (5 mg) prasugrel to evaluate the routine use of dose-adjusted prasugrel in this high-risk subset of patients. Methods: We included 59 elderly patients (≥75 years) treated with Dual Antiplatelet Therapy (DAPT: acetylsalicylic acid (ASA) 100-160 mg + prasugrel 5 mg) after Percutaneous Coronary Interventions (PCI) and undergoing platelet function assessment (by whole blood impedance aggregometry) 30-90 days post-discharge. Results: At a median follow-up of 43 days (interquartile range-IQR: 32-54), high-on treatment residual platelet reactivity (HRPR) occurred in 25 patients (42.4%), who displayed a greater body mass index (BMI) (p=0.02), lower levels of vitamin D (p=0.05) and were more frequently treated with nitrates (p=0.03). After multivariate analysis, BMI was the only independent predictor of prasugrel HRPR, and a BMI >26 was the best cut-off for predicting HRPR (adjusted Odds Ratio - OR=8.6, 95%CI: 2.2-33.9, p=0.002). Conclusion: Among elderly patients receiving DAPT after PCI, HRPR is common with low-dose prasugrel. A greater BMI, especially for values ≥26, is the only independent predictor of HRPR with prasugrel 5 mg.
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MiR-199a-5p Deficiency Promotes Artery Restenosis in Peripheral Artery Disease by Regulating ASMCs Function via Targeting HIF-1α and E2F3
Authors: Duan Liu, Yexiang Jing, Guiyan Peng, Litai Wei, Liang Zheng, Guangqi Chang and Mian WangBackground: Restenosis (RS) poses a significant concern, leading to recurrent ischemia and the potential for amputation following intraluminal angioplasty in the treatment of Peripheral Artery Disease (PAD). Through microRNA microarray analysis, the study detected a significant downregulation of miR-199a-5p within arterial smooth muscle cells (ASMCs) associated with RS. Objective: This research aims to explore the possible function and the underlying mechanisms of miR-199a-5p in the context of RS. Methods: Primary ASMCs were extracted from the femoral arteries of both healthy individuals and patients with PAD or RS. The expression levels of miR-199a-5p were assessed using both qRT-PCR and in situ hybridization techniques. To examine the impacts of miR-199a-5p, a series of experiments were performed, including flow cytometry, TUNEL assay, EdU assay, CCK8 assay, Transwell assay, and wound closure assay. A rat carotid balloon injury model was employed to elucidate the mechanism through which miR-199a-5p mitigated neointimal hyperplasia. Results: MiR-199a-5p exhibited downregulation in RS patients and was predominantly expressed within ASMCs. Elevated the expression of miR-199a-5p resulted in an inhibitory effect of proliferation and migration in ASMCs. Immunohistochemistry and a dual-luciferase reporter assay uncovered that RS exhibited elevated expression levels of both HIF-1α and E2F3, and they were identified as target genes regulated by miR-199a-5p. The co-transfection of lentiviruses carrying HIF-1α and E2F3 alongside miR-199a-5p further elucidated their role in the cellular responses mediated by miR-199a-5p. In vivo, the delivery of miR-199a-5p via lentivirus led to the mitigation of neointimal formation following angioplasty, achieved by targeting HIF-1α and E2F3. Conclusion: MiR-199a-5p exhibits promise as a prospective therapeutic target for RS since it alleviates the condition by inhibiting the proliferation and migration of ASMCs via its regulation of HIF-1α and E2F3.
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Chronic Administration of Red Yeast Rice Mitigates Endothelial Dysfunction in Spontaneously Hypertensive Rats by Inhibiting Oxidative Stress and Endothelial Nitric Oxide Synthase Uncoupling
Authors: Jiunn J. Tan, Dharmani Devi Murugan, Wei Chih Ling, Siew-Keah Lee and Waye Hann KangBackground: Hypertension is associated with endothelial dysfunction. An imbalance in the production of Nitric Oxide (NO) and Reactive Oxygen Species (ROS), leading to impaired NO-cyclic Guanosine Monophosphate (cGMP) pathway, contributes to this disorder. Red Yeast Rice (RYR), produced from the fermentation of rice with Monascus purpureus, is a traditional functional food originating from China. Although recognized for its anti-dyslipidemia properties, there has been growing evidence regarding the anti-hypertensive effects of RYR. However, these studies only focused on its direct and short-term effects. Aim: This study aims to investigate the vasoprotective effects of chronic oral RYR administration using Spontaneously Hypertensive Rats (SHR). Materials and Methods: SHR were randomly divided into 3 groups: SHR - Control; SHR - RYR extract (100 mg/kg/day); SHR - lovastatin (10 mg/kg/day). Wistar-Kyoto Rats (WKY) were used as normotensive controls. All animals were treated for 12 weeks by oral gavage. Systolic Blood Pressure (SBP) was measured weekly (tail-cuff method). Vascular reactivity was determined using isolated rat aortic rings in an organ bath. Aortic ROS, NO, tetrahydrobiopterin (BH4), and cGMP levels were evaluated. Results: Administration of RYR attenuated SBP elevation and enhanced endothelium-dependent vasodilation in aortic rings. In addition, RYR decreased ROS production and significantly improved the level of vascular NO, BH4, and cGMP. Conclusion: In an SHR model, treatment with RYR for 12 weeks exerts an SBP lowering effect that can be attributed to improved vascular function via reduction of oxidative stress, decreased endothelial NO Synthase (eNOS) uncoupling and enhanced NO-cGMP pathway.
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Gut Microbiota Modulation by Selenium and Zinc Enrichment Postbiotic on Dysbiosis Associated with Hypertension
Authors: Laura-Dorina Dinu, Florentina Gatea, Florentina Matei, Cristian Banciu and Emanuel VamanuBackground: Targeting gut dysbiosis to treat chronic diseases or to alleviate the symptoms is a new direction for medical adjuvant therapies. Recently, postbiotics have received considerable attention as they are non-viable probiotic preparations that confer various health benefits to the host without the safety problems associated with using live microbial cells. Objective: The aim of the study is to obtain selenium (Se) and zinc (Zn) enriched Saccharomyces boulardii postbiotic biomass and to analyze its modulation effect because these minerals play an important role in reducing gut dysbiosis linked to cardiovascular (CV) diseases. Method: The effect of the S. boulardii and Se/Zn enriched yeast postbiotics on CV microbial fingerprint was studied in vitro using the gastrointestinal system (GIS 1) and analyzed by microbiological, chemical, and qPCR methods. Result: There was a 2.2 log CFU/mL increase in the total bacterial load after SeZn postbiotic treatment and in the qPCR counts of Firmicutes phyla for both treatments. Beneficial taxa, Bifidobacterium spp. and Lactobacillus spp., as well as Bacteroidesspp. were up to 1.5 log higher after mineral- enriched postbiotic application, while the acetic acid level increased. Conclusion: These preliminary studies highlight the therapeutic potential of using Se/Zn enriched yeast postbiotics as adjuvants for clinical treatments of CV diseases
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Volumes & issues
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Volume 22 (2024)
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Volume 21 (2023)
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Volume 20 (2022)
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Volume 19 (2021)
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Volume 18 (2020)
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Volume 17 (2019)
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Volume 16 (2018)
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Volume 15 (2017)
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Volume 14 (2016)
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Volume 13 (2015)
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Volume 12 (2014)
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Volume 11 (2013)
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Volume 10 (2012)
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Volume 9 (2011)
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Volume 8 (2010)
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Volume 7 (2009)
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Volume 6 (2008)
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Volume 5 (2007)
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Volume 4 (2006)
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Volume 3 (2005)
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Volume 2 (2004)
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Volume 1 (2003)