C1q/TNF-related protein 9 inhibits the cholesterol-induced Vascular smooth muscle cell phenotype switch and cell dysfunction by activating AMP-dependent kinase

Qi Liu; Hui Zhang; Jiale Lin; Ruoxi Zhang; Shuyuan Chen; Wei Liu; Meng Sun; Wenjuan Du; Jingbo Hou; Bo Yu

doi:10.1111/jcmm.13196

C1q/TNF-related protein 9 inhibits the cholesterol-induced Vascular smooth muscle cell phenotype switch and cell dysfunction by activating AMP-dependent kinase

J Cell Mol Med. 2017 Nov;21(11):2823-2836. doi: 10.1111/jcmm.13196. Epub 2017 May 19.

Authors

Qi Liu^{1

2}, Hui Zhang^{1

2}, Jiale Lin^{1

2}, Ruoxi Zhang^{1

2}, Shuyuan Chen^{1

2}, Wei Liu^{1

2}, Meng Sun^{1

2}, Wenjuan Du^{1

2}, Jingbo Hou^{1

2}, Bo Yu^{1

2}

Affiliations

¹ The Key Laboratory of Myocardial Ischemia Organization, Chinese Ministry of Education, Harbin, China.
² Division Department of Cardiology Organization, The Second Affiliated Hospital of Harbin Medical University, 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.

Keywords: AMP-dependent kinase; C1q/TNF-related protein 9; Vascular smooth muscle cell; cholesterol; macrophage-like cells.

MeSH terms

AMP-Activated Protein Kinases / antagonists & inhibitors
AMP-Activated Protein Kinases / genetics*
AMP-Activated Protein Kinases / metabolism
Adiponectin / genetics*
Adiponectin / metabolism
Adiponectin / pharmacology
Cell Adhesion / drug effects
Cell Line
Cholesterol / pharmacology*
Gene Expression Regulation
Glycoproteins / genetics*
Glycoproteins / metabolism
Glycoproteins / pharmacology
Humans
Muscle, Smooth, Vascular / cytology
Muscle, Smooth, Vascular / drug effects
Muscle, Smooth, Vascular / metabolism*
Myeloid Differentiation Factor 88 / genetics
Myeloid Differentiation Factor 88 / metabolism
Myocytes, Smooth Muscle / cytology
Myocytes, Smooth Muscle / drug effects
Myocytes, Smooth Muscle / metabolism*
RNA, Small Interfering / genetics
RNA, Small Interfering / metabolism
Recombinant Proteins / genetics
Recombinant Proteins / metabolism
Recombinant Proteins / pharmacology
Signal Transduction
Toll-Like Receptor 4 / genetics
Toll-Like Receptor 4 / metabolism
Transcription Factor RelA / genetics
Transcription Factor RelA / metabolism
Tumor Necrosis Factor Receptor-Associated Peptides and Proteins

Substances

Adiponectin
C1QTNF9B protein, human
Glycoproteins
MYD88 protein, human
Myeloid Differentiation Factor 88
RNA, Small Interfering
Recombinant Proteins
TLR4 protein, human
Toll-Like Receptor 4
Transcription Factor RelA
Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
Cholesterol
AMP-Activated Protein Kinases
PRKAA1 protein, human