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Published on: February 15, 2022
C1q/TNF-related protein 9 inhibits the cholesterol-induced Vascular smooth muscle cell phenotype switch and cell
Qi Liu1,2, Hui Zhang1,2, Jiale Lin1,2
1The Key Laboratory of Myocardial Ischemia Organization, Chinese Ministry of Education, Harbin, China.
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.
Insights
C1q/TNF-related protein 9 (CTRP9) protects vascular smooth muscle cells from cholesterol damage by reducing inflammation and promoting cholesterol removal, mediated through the AMP-dependent kinase (AMPK) pathway.
Area of Science:
- Biochemistry
- Cell Biology
- Cardiovascular Research
Background:
- Vascular smooth muscle cells (VSMCs) can transform into macrophage-like cells upon cholesterol loading, contributing to atherosclerosis.
- C1q/TNF-related protein 9 (CTRP9), an adipokine, exhibits cardioprotective effects, but its role in cholesterol-induced VSMC damage is unknown.
Purpose of the Study:
- To investigate the protective effects of CTRP9 against cholesterol-induced damage in VSMCs.
- To elucidate the underlying molecular mechanisms of CTRP9's action in VSMCs.
Main Methods:
- VSMCs were loaded with cholesterol and treated with CTRP9.
- Assessed inflammatory factor secretion, monocyte adhesion, cholesterol uptake, and CD68 expression.
- Investigated the Toll-like receptor 4 (TLR4)-MyD88-p65 signaling pathway.
- Utilized siRNA to ablate AMP-dependent kinase (AMPK) α1 expression.
Main Results:
- CTRP9 significantly reversed cholesterol-induced increases in pro-inflammatory factors, monocyte adhesion, cholesterol uptake, and CD68 expression.
- CTRP9 inhibited the activation of the TLR4-MyD88-p65 pathway.
- CTRP9 upregulated proteins involved in cholesterol efflux.
- AMPKα1 ablation abolished CTRP9's protective effects.
Conclusions:
- CTRP9 protects VSMCs from cholesterol damage by suppressing inflammation and enhancing cholesterol efflux.
- The protective mechanism of CTRP9 involves the activation of the AMPK pathway.
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