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.

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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