Incretin hormones as immunomodulators of atherosclerosis

Abstract

Atherosclerosis results from endothelial cell dysfunction and inflammatory processes affecting both macro- and microvasculature which are involved in vascular diabetic complications. Glucagon-like peptide-1 (GLP-1) is an incretin hormone responsible for amplification of insulin secretion when nutrients are given orally as opposed to intravenously and itretains its insulinotropic activity in patients with type 2 diabetes mellitus (T2D). GLP-1 based therapies, such as GLP-1 receptor (GLP-1R) agonists and inhibitors of dipeptidyl peptidase-4, an enzyme that degrades endogenous GLP-1 are routinely used to treat patients with T2D. Recent experimental model studies have established that GLP-1R mRNA is widely expressed in several immune cells. Moreover, its activation contributes to the regulation of both thymocyte and peripheralT cells proliferation and is involved in the maintenance of peripheral regulatory T cells. GLP-1R is also expressed in endothelial and smooth muscle cells. The effect of incretin hormones on atherosclerogenesis have recently been studied in animal models of apolipoprotein E-deficient mice (apoE-/-). These studies have demonstrated that treatment with incretin hormones or related compounds suppresses the progression of atherosclerosis and macrophage infiltration in the arterial wall as well as a marked anti-oxidative and anti-inflammatory effect on endothelial cells. This effect may have a major impact on the attenuation of atherosclerosis and may help in the design of new therapies for cardiovascular disease in patients with type 2 diabetes. © 2012 Alonso, Julián, Puig-Domingo and Vives-Pi.