Adiponectin actions in the cardiovascular system

Abstract

Obesity is strongly associated with the pathogenesis of type 2 diabetes, hypertension, and cardiovascular disease. Levels of the hormone adiponectin are downregulated in obese individuals, and several experimental studies show that adiponectin protects against the development of various obesity-related metabolic and cardiovascular diseases. Adiponectin exhibits favorable effects on atherogenesis, endothelial function, and vascular remodeling by modulation of signaling cascades in cells of the vasculature. More recent findings have shown that adiponectin directly affects signaling in cardiac cells and is beneficial in the setting of pathological cardiac remodeling and acute cardiac injury. Several of these effects of adiponectin have been attributed to the activation of the 5' AMP-activated protein kinase signaling cascade and other signaling proteins. This review will discuss the epidemiological and experimental studies that have elucidated the role of adiponectin in a variety of cardiovascular diseases.

Figure 1

Adiponectin is secreted by adipocytes and has a multiplicity of actions in the cardiovascular system. Adiponectin prevents insulin resistance by enhancing glucose and fatty acid disposal by skeletal muscle. In the heart, adiponectin prevents both pathological hypertrophy and ischemic injury, in part through the activation of AMPK. Adiponectin prevents atherosclerotic progression and intimal hyperplasia by reducing smooth muscle cell proliferation. Similarly, in microvessels and capillaries, adiponectin improves angiogenesis and endothelial function through actions on eNOS and blood vessel growth pathways.

Figure 2

Signaling pathways downstream of adiponectin in cells of the cardiovascular system. Adiponectin has anti-inflammatory effects due to suppression of NFκB signaling in monocytes/macrophages and also reduces the progression of atherosclerotic lesions through suppression of NFκB in endothelial cells. In addition, adiponectin signals through the AMPK pathway to reduce endothelial cell apoptosis and to promote nitric oxide production. In the heart, adiponectin activates AMPK and decreases the hypertrophic response through suppression of protein synthesis. COX2 activation by adiponectin decreases expression of TNFα in the heart. Finally, adiponectin acts in smooth muscle cells to prevent atherosclerotic proliferation and migration of smooth muscle cells.