Integrin signaling in atherosclerosis

Atherosclerosis, a chronic lipid-driven inflammatory disease affecting large arteries, represents the primary cause of cardiovascular disease in the world. The local remodeling of the vessel intima during atherosclerosis involves the modulation of vascular cell phenotype, alteration of cell migration and proliferation, and propagation of local extracellular matrix remodeling. All of these responses represent targets of the integrin family of cell adhesion receptors. As such, alterations in integrin signaling affect multiple aspects of atherosclerosis, from the earliest induction of inflammation to the development of advanced fibrotic plaques. Integrin signaling has been shown to regulate endothelial phenotype, facilitate leukocyte homing, affect function, and drive smooth muscle fibroproliferative remodeling. In addition, integrin signaling in platelets contributes to the thrombotic complications that typically drive the clinical manifestation of cardiovascular disease. In this review, we examine the current literature on integrin regulation of atherosclerotic plaque development and the suitability of integrins as potential therapeutic targets to limit cardiovascular disease and its complications.