Abstract
Vascular smooth muscle cells (VSMCs) switch to macrophage‐like cells after cholesterol loading, and this change may play an important role in the progression of atherosclerosis. C1q/TNF‐related protein 9 (CTRP9) is a recently discovered adipokine that has been shown to have beneficial effects on glucose metabolism and vascular function, particularly in regard to cardiovascular disease. The question of whether CTRP9 can protect VSMCs from cholesterol damage has not been addressed. In this study, the impact of CTRP9 on cholesterol‐damaged VSMCs was observed. Our data show that in cholesterol‐treated VSMCs, CTRP9 significantly reversed the cholesterol‐induced increases in pro‐inflammatory factor secretion, monocyte adhesion, cholesterol uptake and expression of the macrophage marker CD68. Meanwhile, CTRP9 prevented the cholesterol‐induced activation of the TLR4–MyD88–p65 pathway and upregulated the expression of proteins important for cholesterol efflux. Mechanistically, as siRNA‐induced selective gene ablation of AMPKα1 abolished these effects of CTRP9, we concluded that CTRP9 achieves these protective effects in VSMCs through the AMP‐dependent kinase (AMPK) pathway.
Highlights
Atherosclerosis is a leading cause of morbidity and mortality around the world [1, 2]
It is widely accepted that the majority of foam cells are derived from macrophages that originate from circulating monocytes; recent research has provided a different vision for the origin of some macrophages; Vascular smooth muscle cells (VSMCs) that become loaded with cholesterol have been shown to lose VSMC markers such as smooth muscle a-actin (ACTA2) and assume the appearance of macrophages expressing macrophage-specific markers such as CD68 [5, 6]
The existence of smooth muscle foam cells in human atherosclerosis has been well documented [29]; recent studies have demonstrated that cholesterol loading downregulates VSMC contractile proteins, but upregulates macrophage markers, which indicates a switch of VSMCs to macrophage-like foam cells [5, 8, 30]
Summary
Atherosclerosis is a leading cause of morbidity and mortality around the world [1, 2]. Atherosclerotic plaque lumen-narrowing and rupture-induced thrombosis or obstruction of the coronary artery are the biggest causes of the sudden and unpredictable onset of acute coronary syndrome [3, 4]. It is widely accepted that the majority of foam cells are derived from macrophages that originate from circulating monocytes; recent research has provided a different vision for the origin of some macrophages; VSMCs that become loaded with cholesterol have been shown to lose VSMC markers such as smooth muscle a-actin (ACTA2) and assume the appearance of macrophages expressing macrophage-specific markers such as CD68 [5, 6]. In human atherosclerotic plaques, 30–40 percent of cells positive for the macrophage marker CD68 are VSMC-derived [5]. The athero-protective layer, a fibrous cap, consists of ACTA2-positive cells that surround the atherosclerotic plaque.
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