Protective Effect of Irisin on Atherosclerosis via Suppressing Oxidized Low Density Lipoprotein Induced Vascular Inflammation and Endothelial Dysfunction

Abstract

Irisin, a newly discovered myokine, is considered as a promising candidate for the treatment of metabolic disturbances and cardiovascular diseases. In the present study, we used two animal models, apolipoprotein E-deficient mice fed on a high-cholesterol diet and a mouse carotid partial ligation model to test the anti-atherosclerotic effect of irisin. Irisin treatment (0.5 μg/g body weight/day) significantly reduced the severity of aortic atherosclerosis in apolipoprotein E-deficient mice fed on a high-cholesterol diet and suppressed carotid neointima formation in a carotid partial ligation model. It was associated with decreased inflammation and cell apoptosis in aortic tissues. In addition, in a cell culture model, irisin restored ox-LDL-induced human umbilical vein endothelial cell dysfunction by reducing the levels of inflammatory genes via inhibiting the reactive oxygen species (ROS)/ p38 MAPK/ NF-κB signaling pathway activation and inhibiting cell apoptosis via up-regulating Bcl-2 and down-regulating Bax and caspase-3 expression. Our study demonstrated that irisin significantly reduced atherosclerosis in apolipoprotein E-deficient mice via suppressing ox-LDL-induced cell inflammation and apoptosis, which might have a direct therapeutic effect on atherosclerotic diseases.

Irisin Regulates Heme Oxygenase-1/Adiponectin Axis in Perivascular Adipose Tissue and Improves Endothelial Dysfunction in Diet-Induced Obese Mice

“…It has been suggested that irisin seems to be beneficial for many metabolic diseases including diabetes and obesity through promoting the browning of white adipocytes [25]. Recent studies demonstrated that altered irisin levels are related to endothelial function [26, 27]. Irisin improves endothelial function and atherosclerosis in diabetic mice [27].…”

Daily melatonin protects the endothelial lineage and functional integrity against the aging process, oxidative stress, and toxic environment and restores blood flow in critical limb ischemia area in mice

“…In fact, abundant data have shown that the initiation and propagation of endothelial cell (EC) dysfunction in the coronary artery are the fundamental mechanism for the development of arteriosclerosis, followed by plaque formation and ultimately, plaque fissuring and rupture, resulting in acute obstructive syndrome . A large number of studies have reported that inflammation, generations of oxidative stress/free radicals, and oxidized low‐density lipoprotein (LDL) as well as aging are crucial contributors to the initiation and propagation of EC dysfunction . Thus, early interventions (ie, primary prevention) using health supplements to prevent and alleviate endothelial dysfunction may be a feasible approach.…”

Are Heart Muscle Irisin Levels and FNDC5 Gene Expression Regulated by Endurance and Resistance Exercises?

“…Therefore, one of the mechanisms through which the heart benefits from physical activities through the increase of irisin levels might be the major role irisin plays in maintaining the functioning of endothelial cells. Irisin has thus been known as a potential medicinal aid in treating atherosclerosis (18).…”

“…Conversely, regular physical exercise is proportionate to atherosclerosis and the occurrence of primary and secondary cardiovascular attacks, although the mechanisms of physical exercise leading to prevention of atherosclerosis are not clearly known yet (18). Nonetheless, these are perhaps, a combination of optimal energy balance, fatness limitation and inflation, which is the potential result of the secretion of myokines (5).…”

“…In this regard, irisin is a myokine which is involved in the development of atherosclerosis (1) and thus can help in the treatment of atherosclerosis, as it is a potential treatment goal (18).…”