IGF-1 and cardiovascular disease

Abstract

Atherosclerosis is an inflammatory arterial pathogenic condition, which leads to ischemic cardiovascular diseases, such as coronary artery disease and myocardial infarction, stroke, and peripheral arterial disease. Atherosclerosis is a multifactorial disorder and its pathophysiology is highly complex. Changes in expression of multiple genes coupled with environmental and lifestyle factors initiate cascades of adverse events involving multiple types of cells (e.g. vascular endothelial cells, smooth muscle cells, and macrophages). IGF-1 is a pleiotropic factor, which is found in the circulation (endocrine IGF-1) and is also produced locally in arteries (endothelial cells and smooth muscle cells). IGF-1 exerts a variety of effects on these cell types in the context of the pathogenesis of atherosclerosis. In fact, there is an increasing body of evidence suggesting that IGF-1 has beneficial effects on the biology of atherosclerosis. This review will discuss recent findings relating to clinical investigations on the relation between IGF-1 and cardiovascular disease and basic research using animal models of atherosclerosis that have elucidated some of the mechanisms underlying atheroprotective effects of IGF-1.

Figure.. Cell-specific mechanisms underlying atheroprotective effect of IGF-1.

Cumulative reports of in vitro and in vivo investigations suggest that IGF-1 is suppressive to the recruitment of monocytes/macrophages to atherosclerotic plaques, production of proinflammatory cytokines, conversion of macrophages into lipid-laden foam cells, and extracellular matrix degradation. On the other hand, IGF-1 promotes smooth muscle cell (SMC) migration, proliferation and SMC-dependent matrix deposition. These cell-specific mechanisms may contribute to IGF-1-induced reduction in plaque burden and increase in plaque stability.