Abstract
Irisin is a newly discovered myokine that links exercise with metabolic homeostasis. It is involved in modest weight loss and improves glucose intolerance. However, the direct effects and mechanisms of irisin on vascular endothelial cells (ECs) are not fully understood. In the current study, we demonstrated that irisin promoted Human Umbilical Vein Endothelial Cell (HUVEC) proliferation. It was further demonstrated that this pro-proliferation effect was mediated by irisin-induced activation of extracellular signal–related kinase (ERK) signaling pathways. Inhibition of ERK signaling with U0126 decreased the pro-proliferation effect of irisin on HUVECs. It was also demonstrated that irisin reduced high glucose-induced apoptosis by up-regulating Bcl-2 expression and down-regulating Bax, Caspase-9 and Caspase-3 expression. In summary, these results suggested that irisin plays a novel role in sustaining endothelial homeostasis by promoting HUVEC proliferation via the ERK signaling pathway and protects the cell from high glucose-induced apoptosis by regulating Bcl-2,Bax and Caspase expression.
Highlights
Many vascular diseases are caused by endothelial cell (EC) injury and dysfunction, which occurs in chronic metabolic diseases such as metabolic syndrome and type II diabetes mellitus [1,2]
Effect of irisin on Human Umbilical Vein Endothelial Cell (HUVEC) proliferation To investigate the role of irisin on HUVEC proliferation, [3H]
To assess the actual cell number changes, the effects of irisin on HUVEC proliferation was detected by direct cell counting
Summary
Many vascular diseases are caused by endothelial cell (EC) injury and dysfunction, which occurs in chronic metabolic diseases such as metabolic syndrome and type II diabetes mellitus [1,2]. In many chronic metabolic diseases, vascular endothelial integrity is affected by EC proliferation and apoptosis, which assures blood vessel function [3]. Recent studies discovered that type 2 diabetic patients displayed significantly lower levels of circulating irisin compared with non-diabetic control subjects [6,7]. Circulating irisin levels were decreased in patients with chronic kidney disease (CKD) and were independently associated with high-density lipoprotein cholesterol levels [8]. A new study demonstrated that pharmacological irisin concentrations promote mouse H19-7 HN cell proliferation via the STAT3 signaling pathway [9]. This finding suggests that irisin may have a pro-proliferation effect in addition to its role in regulating metabolic homeostasis. No previous studies have evaluated whether irisin may directly regulate human EC
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