Current Vascular Pharmacology - Volume 15, Issue 4, 2017

Background: Gut microbiota is increasingly recognized as a powerful regulator of host physiology. Most of its effects are mediated through metabolites acting as energy sources, signaling receptor ligands and substrates for host enzymes. Owing to the meta-stability and high amenability of the gut microbiota to modification by diet and environment predicting specific gut microbes or its metabolites responsible for different host metabolic states is often confounded. Methods: The Pubmed was searched for research articles on gut microbiota and cardiovascular disease. Results: The searched articles reported a direct role of gut microbes in cardiovascular disorders (CVD). The interaction among gut microbial metabolism (through breakdown of certain dietary nutrients like choline), host immune system and lipid metabolism generate conditions that promote atherosclerosis development. Importantly, components of this interactive system can be explored to identify points of intervention in the path of disease development. Based on this strategies targeting gut microbial composition and activity are being explored as therapies against CVD. Use of archaebiotics and 3,3-dimethyl- 1-butanol aiming to reduce TMA (trimethylamine) conversion to TMAO (trimethylamine-N-oxide) and high fibre diets to reduce TMA precursors while simultaneously selecting for beneficial gut bacteria are attractive anti-atherogenic approaches. Conclusion: Success of these approaches in humans however, requires extensive research.

Cells constantly adapt to external humoral cues like cytokines and hormones, but practically most cellular behavior is under locally guided control via cell–cell interactions. Galectins (Gals) are one of the most prominent members of the group of molecules involved in this intercellular signaling. They are the family of β-galactoside specific lectins and consist of 15 different types, each with a specific function. They play crucial role in the immune system, inflammation, wound healing and carcinogenesis. In recent times, the role of Gals in the development of cardiovascular disease (CVD) has gained attention. Gals have been reported to act ambiguously by both relieving ischemia and accelerating atherosclerosis. Atherosclerosis can ultimately lead to myocardial infarction or ischemic stroke, which are both associated with Gals. There is also a role for Gals in the development of myocarditis by their influence on inflammatory processes. Moreover, Gal acts as a biomarker for the severity of myocardial ischemia and heart failure (HF). This review summarizes the association between Gals and the development and pathogenesis of CVD like atherosclerosis, stroke, myocardial infarction, and HF. A comprehensive outline of the association between Gals and more general mechanisms such as angiogenesis, arteriogenesis and atherosclerosis has also been provided. Modulation of Gal signaling holds great promise for the treatment of CVD as evident from preclinical studies.

Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by thrombosis and/or pregnancy morbidity with persistent levels of antiphospholipid antibodies (aPLs). The development of thrombosis in APS is mediated by aPLs and contributes to the high mortality rate in APS patients. However, although APS has been reported for more than 30 years, there has been no optimal regimen for its prevention or for the management of thrombosis, mainly because the mainstay treatment strategies for managing APS are not targeted towards aPL-mediated thrombotic pathophysiology. Instead, the treatments commonly used are aimed at general thrombotic disorders. Warfarin is the most commonly used vitamin K antagonist (VKA), in addition to anti-platelet medications, such as aspirin and clopidogrel. Over the last decade, novel non-VKA oral anticoagulants, including rivaroxaban, apixaban and dabigatran, as well as immunomodulatory agents, such as rituximab, eculizumab, hydroxychloroquine, statins and sirolimus, have also been used. In this review, we discuss the current treatment strategies and future treatment outlook for thrombotic APS.

There has been an increasing interest in the usage of natural products for the prevention and treatment of chronic diseases such as cardiovascular disease (CVD). Regular consumption of fruits, vegetables and whole grains has been shown to be negatively correlated with the risk of CVDs. These foods provide a diversity of nutrients and different bioactive compounds including phytochemicals, vitamins, minerals and fibers which play critical roles in the sustainability of optimal cardiovascular health. Plant-based foods or a nutritional cure are gradually being integrated into medical practice for CVD management partly due to the supporting experimental studies, clinical trials and epidemiological studies. These products have anti-oxidant, anti-inflammatory, hypoglycemic, hypolipidemic, hypotensive, anti-atherosclerotic, anti-thrombotic and hypocholesterolemic effects, depending on the dosage in cell and tissue cultures, animal models as well as in humans. The present review considers some novel ideas on some major phytochemicals which have been suggested to have protective and therapeutic potential in CVD. The data presented in this work have been compiled from studies that have mostly been carried out in recent years.

Angiogenesis is defined as the physiological process by which new blood vessels develop from pre-existing vessels; either by sprouting or intussusception. Inhibition of angiogenesis is one of the most encouraging strategies to manage the growth and metastasis of cancers. The functional and proliferative status of blood vessels is regulated by the balance between various key molecules that either stimulate or inhibit angiogenesis. During quiescence, the “angiogenic switch” is “off”. However, during tumour development pro-angiogenic factors such as vascular endothelial growth factor (VEGF), basic and acidic fibroblast growth factor, tumour necrosis factor-α and interleukin-1 are pathologically enhanced. Persistent growth of tumour directed capillary networks creates a favourable microenvironment, promoting cancer growth, progression and metastasis. VEGF, particularly VEGF-A, is a key angiogenic factor. Targeting VEGF, its receptors and the downstream signaling cascade, is a viable strategy to prevent tumour growth and metastasis. The present review discusses the role of VEGF in tumour angiogenesis and the current understanding of anti-VEGF therapies as well as refractoriness of anti-angiogenesis cancer therapy.

In diabetic patients, accelerated glycation process causes increased oxidative stress and chronic hyperglycaemia that play a vital role in the diabetic complications. Extensive intracellular and extracellular generation of these glycated products finally form advanced glycation end products (AGEs). The accumulation of AGEs is related with the intensive risk for microvascular and macrovascular injuries for diabetic patients. Therefore, formation of AGEs results from the condensation of reducing sugars with biomolecules like nucleic acids, proteins, and lipids which potentially alter their function. Effect of AGEs formation is also related with the cross-linking that promotes vascular stiffness which modifies the vascular structure and long-life function of proteins. Formation of AGEs may also activate specific receptors, like receptor for AGEs (RAGEs) that induce the intracellular signaling which enhance the oxidative stress and also the amplification of key pro-sclerotic and pro-inflammatory cytokines. From last few decades, a huge number of pre-clinical studies related with the AGEs formation in the diabetic patients have been performed. The target for such trials was the formation and degradation of AGEs, and its interaction with RAGEs. This review focuses on the mechanism how these AGEs exert detrimental nuisance in the diabetes, as well as deal with existing strategies to disrupt the action or formation of AGEs. Therefore, the unseen role of both the early and advanced stage glycation in the diabetic Vasculopathy is described. We have also illustrated how the glycation inhibition results in the delay of the development of vascular complications in diabetic patients.

Despite recent advances in medical research, the incidence of diabetes and cardiovascular disease (CVD)-induced fatal events is increasing. The literature point towards several co-occurring pathways that could lead to terminal complications related with these diseases. Different pathophysiological alterations such as hyperglycaemia, hyperinsulinaemia, insulin resistance, obesity, endothelial dysfunction and oxidative stress lead to the initiation and progression of atherosclerotic plaques. In view of the continuous rise in fatal events and overlapping pathological conditions associated with CVD and diabetes, there is a critical need to develop a common treatments against these diseases. The present review highlights the possible use of common drugs that could target diabetes and associated CVD.

Low-density lipoprotein cholesterol (LDL-C) is a well-established major cardiovascular (CV) risk factor supported by clinical evidence showing decreased atherosclerotic disease events when LDL-C is therapeutically lowered. A reasonable approach is to tailor each patient’s LDL-C target level depending on the initial LDL-C level and the perceived risk. Multiple clinical entities such as the newborn, hypobetalipoproteinemia, proprotein convertase subtilisin/kexin type 9 (PCSK9) missense mutations, and an unexpected excess response to a statin or other medications, are associated with very low LDL-C levels in otherwise healthy individuals. Therefore, an issue of major interest to clinicians who buy into “lower is better” for LDL-C in the high-risk CV patient is how low can and should the LDL-C be taken? Available information is discussed and placed into context. A definite safe lowest LDL-C level cannot be specified but there appears to be support that a level as low as 20 mg/dL (0.52 mmol/l) can be justified in the highest CV risk patients with extensive atherosclerosis where plaque stabilization and regression are necessary.

Background and Objectives: Obesity is often associated with insulin resistance (IR). We considered different IR indexes: the Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) index, the two specimen (0 and 120 min) oral glucose tolerance test Matsuda Index (MI) and the Homeostasis Model Assessment-Adiponectin (HOMA-AD) index. These IR indexes were compared with indicators of the cardiometabolic profile. Method: This cross-sectional study enrolled 60 obese individuals without previous history of diabetes. Anthropometrical, ultrasound and laboratory examinations were conducted. Results: All 3 indexes significantly correlated with indicators of central obesity, systolic and diastolic blood pressure, inflammation parameters, liver enzymes, HbA1c and some lipid parameters. The majority of correlation coefficients were the highest for HOMA-AD, but only the difference in correlation with waist circumference comparing with MI was statistically significant. HOMA-IR directly, and MI indirectly, significantly correlated with age, while HOMA-AD significantly directly correlated with the mean carotid artery intima media thickness (CAIMT). MI showed the best performances in predicting non-alcoholic fatty liver disease and pathologically increased CAIMT; HOMA-AD was the best in predicting metabolic syndrome, while HOMA-IR demonstrated the poorest performances in the prediction of all 3 conditions. There were no statistically significant differences in predicting performances of the analysed indexes. Conclusion: The HOMA-AD and MI are not superior compared with the HOMA-IR, in the identification of obese individuals with a proatherogenic cardiometabolic profile.

Objective: Excessive activated proinflammatory cytokines may promote extracellular matrix alterations which induce adverse left ventricular remodeling in systolic heart failure (SHF). We sought to identify whether high-sensitivity C-reactive protein (hsCRP) levels were independently associated with SHF. Methods: In our retrospective case-control study, 2236 subjects were included, and 260 patients had SHF. Blood sample collection, clinical laboratory tests, electrocardiogram and echocardiography examinations were performed. The questionnaires were completed by professional interviews. Results: In 2236 subjects, the prevalence rate of SHF were 1.7, 1.8, 8.4 and 32.6% between hsCRP concentrations (<1 mg/L, ≥1 to <3 mg/L, ≥3 to <10 mg/L and ≥10 mg/L, respectively) (p=0.000). hsCRP concentrations (<1 mg/L, ≥1 to <3 mg/L, ≥3 to <10 mg/L and ≥10 mg/L) were associated in a linear trend with N-terminal pro-brain natriuretic peptide (NT-proBNP, p=0.000) and left ventricular ejection fraction (LVEF, p=0.000). hsCRP was also significantly related to NT-proBNP, LVEF and SHF (r=0.232, p=0.000; r=-0.358, p=0.000 and r=0.413, p=0.000, respectively). In logistic regression model, after adjusting for heart failure risk factors, compared with the low concentration of hsCRP (<1 mg/L), the high concentration of hsCRP (≥10 mg/L) was significantly independently associated with SHF (odds ratio = 10.78 [1.303 to 89.10], p=0.027). Conclusion: Low to high concentration of hsCRP showed a linear trend association with SHF. A high concentration of hsCRP was independently associated with SHF.