The Emerging Roles of Leptin and Ghrelin in Cardiovascular Physiology and Pathophysiology

Abstract

Leptin and ghrelin are novel peptide hormones which are counter-regulatory in the central control of appetite. More recently, it has become clear that these hormones have a range of effects on the cardiovascular system. Leptin increases sympathetic activity, producing a pressor effect when acting on the central nervous system. However, leptin produces vasodilation by an endothelium-dependent mechanism peripherally. Ghrelin decreases sympathetic activity and has a depressor effect when acting on the central nervous system. Peripherally, ghrelin produces vasodilation by an endothelium-independent mechanism. Ghrelin improves left ventricular function and cardiac cachexia in heart failure. Leptin may contribute to cardiac cachexia, and to obesity-related cardiomyopathy by a variety of mechanisms. Leptin has pro-inflammatory, proliferative and calcification promoting effects in the vasculature. Ghrelin has recently been shown to be anti-inflammatory in the vasculature. Leptin may also produce a pro-thrombotic state through stimulation of platelet aggregation and inhibition of coagulation and fibrinolysis. The evidence for and against these effects as well as their pathophysiological significance in obesity hypertension, heart failure, atherosclerosis and thrombosis are discussed.

Plasma Ghrelin Levels Are Associated with Coronary Microvascular and Endothelial Dysfunction in Peritoneal Dialysis Patients

“…Leptin was also reported to stimulate calcification of endothelial cells in vitro, which may indicate an increased risk of atherosclerosis. [23,36] Although previous studies reported the association between plasma leptin levels and ED in diabetic patients, [34] such an association was not noted in the present study, in which the diabetics were excluded.…”

“…[2,4,23] In the present study, plasma ghrelin levels were significantly higher in patients with normal coronary microvascular and endothelial functions as compared to patients with ED. Although not statistically significant because of the low patient number, a weak correlation also existed between serum ghrelin levels and CFR values.…”

Adipocyte-derived factors suppress heart contraction

“…Leptin has been suggested to have a role in cardiovascular system physiology and pathophysiology. 17 The effect of leptin on cardiac physiology, however, is controversial. Although high doses of leptin (10-1000 nmol l À1 ) seem to directly suppress cardiac contraction in isolated cardiomyocytes, 16 physiologically relevant concentrations (25 ng ml À1 ) abolish the negative inotropic effect of IL-1b, 18 suggesting a potential role of leptin in modulating proinflammatory effects in the heart.…”

Influence of ghrelin gene polymorphisms on hypertension and atherosclerotic disease

“…2, 3 Moreover, there is increasing evidence for a cardiovascular function of ghrelin. Ghrelin has been postulated to exert a protective effect against atherosclerosis by anti-inflammatory, 4 vasodilatory 5 and antioxidant effects, 4 as well as through improved endothelial function. 6 Furthermore, a radiolabeled ghrelin [ 125 I-His9] has been shown to bind to the heart and peripheral vascular tissues.…”