Role of adipokines in cardiovascular disease

The discovery of leptin in 1994 sparked dramatic new interest in the study of white adipose tissue. It is now recognised to be a metabolically active endocrine organ, producing important chemical messengers – adipokines and cytokines (adipocytokines). The search for new adipocytokines or adipokines gained added fervour with the prospect of the reconciliation between cardiovascular diseases (CVDs), obesity and metabolic syndrome. The role these new chemical messengers play in inflammation, satiety, metabolism and cardiac function has paved the way for new research and theories examining the effects they have on (in this case) CVD. Adipokines are involved in a ‘good–bad’, yin–yang homoeostatic balance whereby there are substantial benefits: cardioprotection, promoting endothelial function, angiogenesis and reducing hypertension, atherosclerosis and inflammation. The flip side may show contrasting, detrimental effects in aggravating these cardiac parameter

Chemerin in human cardiovascular disease

Adipose tissue, initially known only for storing excess fat, produces a number of active cytokine-like hormones, collectively known as adipokines or adipocytokines. These molecules are further known to elicit auto-, para- and endocrine functions in the body. In healthy bodies, the cardiovascular endothelium maintains vascular health by critically controlling the interplay between various factors. However, in diseased states such as obesity, owing to numerous metabolic malfunctions, this vascular homeostasis is disrupted. The dysregulated metabolic stimuli perturb vascular homeostasis via initiating or exacerbating the pre-existing inflammatory processes. These inflammatory processes further recruit immune cells to the site of injury, alter cell adhesion molecules expression, and reduce Nitric Oxide levels. These altered mechanisms result in increased blood pressure, endothelial cell migration, proliferation, and apoptosis. In this review article, we aim to evaluate the current literature in understanding the role of Chemerin in vascular health and furthermore, its role in maintaining vascular homeostasis with respect to inflammation, obesity and associated Metabolic Syndrome (MetS) risk factors. For over fifteen years, a growing body of research has been published studying chemerin in the disease states associated with obesity, MetS and cardiovascular disease. Chemerin appears to form an integral link between obesity and related dysfunctional cardiometabolic states as well as in inflammation and immune-system related complications. These combine to suggest a significant Chemerin role in human vascular health and disease

Metformin increases the novel adipokine cartonectin/CTRP3 in women with polycystic ovary syndrome

Recently cartonectin was reported as a novel adipokine, with lower levels in diet-induced obese mice, glucose-lowering effects, and antiinflammatory and cardioprotective properties. Polycystic ovary syndrome (PCOS) is a proinflammatory state associated with obesity, diabetes, dyslipidemia, and cardiovascular complications. Objectives: The objective of the study was to investigate cartonectin levels and regulation in sera and adipose tissue (AT) as well as the effects of metformin of women with PCOS and control subjects. Design: This was a cross-sectional study [PCOS (n = 83) and control (n = 39) subjects]. Real-time PCR and Western blotting were used to assess mRNA and protein expression of cartonectin. Serum cartonectin was measured by an ELISA. Results: Serum and omental adipose tissue cartonectin were significantly lower in women with PCOS compared with control subjects (P < .05 and P < .01, respectively). Furthermore, cartonectin showed a significant negative association with body mass index, waist to hip ratio, glucose, insulin, total cholesterol, low-density lipoprotein-cholesterol, triglycerides, High sensitivity C-reactive protein (hs-CRP) and intima-media thickness (P < .05 and P < .01, respectively); in multiple regression analyses, triglycerides (P =.040) and hs-CRP (P = .031) were predictive of cartonectin levels (P < .05). After 6 months of metformin treatment, there was an associated increase in serum cartonectin (P < .05). Importantly, changes in hs-CRP were significantly negatively correlated with changes in serum cartonectin (P = .033). Finally, cartonectin protein production and secretion into conditioned media were significantly increased by metformin in control human omental AT explants (P < .05)

Functional Cardiac Orexin Receptors: Role of Orexin-B/Orexin 2 Receptor in Myocardial Protection

Orexins/hypocretins exert cardiovascular effects which are centrally mediated. In this study we tested whether orexins and their receptors may also act in an autocrine/paracrine manner in the heart exerting direct effects. Quantitative RT-PCR, immunohistochemical and Western blot analyses revealed that the rat heart expresses orexins and orexin receptors. In isolated rat cardiomyocytes, only orexin-B (OR-B) caused an increase in contractile shortening, independent of diastolic or systolic calcium levels. A specific orexin receptor-2 (OX2R) agonist ([Ala11, D-Leu15]-Orexin B) exerted similar effects as OR-B, whereas a specific OX1R antagonist (SB-408124) did not alter the responsiveness of OR-B. Treatment of the same model with OR-B resulted in a dose-dependent increase of myosin light chain and troponin-I phosphorylation. Following ischaemia/reperfusion in the isolated Langendorff perfused rat heart model, OR-B, but not OR-A, exerts a cardioprotective effect; mirrored in an in vivo model as well. Unlike OR-A, OR-B was also able to induce ERK1/2 and Akt phosphorylation in rat myocardial tissue and ERK1/2 phosphorylation in human heart samples. These findings were further corroborated in an in vivo rat model. In human subjects with heart failure, there is a significant negative correlation between the expression of OX2R and the severity of the disease clinical symptoms, as assessed by the New York Heart Association (NYHA) functional classification. Collectively, we provide evidence of a distinct orexin system in the heart that exerts a cardioprotective role via an OR-B/OX2R pathway