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

Miao Jiang,Haibo Song,Qi Wu,Zheng Zhou,Yuzhu Zhang,Mingxiang Zhang,Xingli Wang,Fang Wang,Dongqi Tang,Lei Shao,Lijun Yang,Fei Wu,Wen Zhang,Liang Li,Shiwu Li,Qian Mu,Shang-Zhong Xu,Yuan Zhang

doi:10.1371/journal.pone.0158038

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.

Highlights

Atherosclerosis, the primary cause of coronary artery disease and stroke, is the leading cause of death in the developed world [1, 2]
In the carotid partial ligation model (Fig 2A), the neointima formation in apolipoprotein E (Apo E)-deficient mice treated with irisin (1.55 ± 0.26×104 μm2) for 4 weeks was significantly decreased compared with control subjects (3.50 ± 0.10×104 μm2) receiving normal saline (NS) (Fig 2B and 2C)
These results suggest that irisin can inhibit atherosclerosis and neointima formation in Apo Edeficient mice

Summary

Introduction

Atherosclerosis, the primary cause of coronary artery disease and stroke, is the leading cause of death in the developed world [1, 2]. The pathophysiological mechanisms and the etiology of PLOS ONE | DOI:10.1371/journal.pone.0158038. Irisin Inhibits Atherosclerosis atherosclerosis are rather complex [3], among which endothelial dysfunction and inflammation play a critical role [4]. Various risk factors can induce endothelial injury which contributes to the initiation and progression of atherosclerosis [1, 5,6,7]. The inflammatory responses to endothelial damage are followed by the development of vascular lesions in the blood vessels [8]. Prevention of endothelial injury could be an important therapeutic target in the treatment of atherosclerotic cardiovascular diseases

Methods

Results

Conclusion