C1q/TNF-related protein-1: an adipokine marking and promoting atherosclerosis.

Abstract

AIMS:

We investigated the association of the adipokine C1q/TNF-related protein (CTRP) 1 with coronary artery disease (CAD), and the biological vascular effects of CTRP1.

METHODS AND RESULTS:

We analysed CTRP1 levels in sera of CAD patients (n = 451) and non-CAD controls (n = 686), and in coronary endarterectomy specimens (n = 32), non-atherosclerotic internal mammary arteries (n = 26), aortic atherosclerotic plaques (n = 15), and non-atherosclerotic aortic samples (n = 10). C1q/TNF-related protein-levels were higher in sera, endarterectomy specimens, aortic atherosclerotic plaques, and peripheral blood mononuclear cells (PBMCs) from CAD patients compared with controls, and were related to CAD severity. The production of CTRP1 was profusely induced by inflammatory cytokines and itself caused a concentration-dependent expression of adhesion molecules and inflammatory markers in human endothelial cells, human peripheral blood monocytes, and THP-1 cells. C1q/TNF-related protein-1 induced p38-dependent monocyte-endothelium adhesion in vitro and the recruitment of leucocytes to mesenteric venules in C57BL/6 mice. Immunohistochemistry of atherosclerotic femoral arteries exhibited CD68 and VE-cadherin loci-associated increased CTRP1 expression in plaques. Compared with saline, intraperitoneal injection of recombinant CTRP1 protein (200 μg/kg) every other day promoted atherogenesis in apoE(-/-) mice at 24 weeks. However, pro-atherogenic effects were significantly attenuated in CTRP1(-/-)/apoE(-/-) double-knockout mice compared with apoE(-/-) mice, with a consistent decrease in vascular adhesion molecule, phospho-p38 and TNF-α expression and macrophage infiltration in plaque in CTRP1(-/-) and double-knockout mice. Tumour necrosis factor-α-induced expression of adhesion molecules and cytokines were lower in primary endothelial cells and macrophages from CTRP(-/-) mice than in those from C57BL/6 mice.

CONCLUSION:

C1q/TNF-related protein-1 is a marker of atherosclerosis in humans and promotes atherogenesis in mice.

• Authors: Lin Lu, Rui Yan Zhang, Xiao Qun Wang, Zhu Hui Liu, Ying Shen, Feng Hua Ding, Hua Meng, Ling Jie Wang, Xiao Xiang Yan, Ke Yang, Hai Bo Wang, Li Jin Pu, Qi Zhang, Qiu Jing Chen, Raffaele De Caterina, Wei Feng Shen
• Journal: European heart journal (Eur Heart J) Vol. 37 Issue 22 Pg. 1762-71 (Jun 07 2016) ISSN: 1522-9645 [Electronic] England
• PMID: 26705391 (Publication Type: Journal Article)
• Copyright: Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: [email protected].

Chemical References

• Adipokines
• Antigens, CD
• Apolipoproteins E
• C1QTNF1 protein, human
• CTRP1 protein, mouse
• Cadherins
• Proteins
• cadherin 5

Topics

• Adipokines
• Animals
• Antigens, CD
• Apolipoproteins E
• Atherosclerosis
• Cadherins
• Humans
• Leukocytes, Mononuclear
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Proteins