C-reactive protein derived from perivascular adipose tissue accelerates injury-induced neointimal hyperplasia

Jia-Yuan Chen,Yong Xie,Xiao-Lin Zhu,Wen-Hao Liu,Hai-Feng Zhang,Qiong Qiu,Ru Ying,Zhi-Teng Chen,Xiaoqiao Wang,Jing-Feng Wang,Yang-Xin Chen,Mao-Xiong Wu

doi:10.1186/s12967-020-02226-x

Abstract

AimInflammation within the perivascular adipose tissue (PVAT) in obesity plays an important role in cardiovascular disorders. C-reactive protein (CRP) level in obesity patients is significantly increased and associated with the occurrence and progression of cardiovascular disease. We tested the hypothesis CRP derived from PVAT in obesity contributes to vascular remodeling after injury.MethodsA high-fat diet (HFD) significantly increased CRP expression in PVAT. We transplanted thoracic aortic PVAT from wild-type (WT) or transgenic CRP-expressing (CRPTG) mice to the injured femoral artery in WT mice.ResultsAt 4 weeks after femoral artery injury, the neointimal/media ratio was increased significantly in WT mice that received PVAT from CRPTG mice compared with that in WT mice that received WT PVAT. Transplanted CRPTG PVAT also significantly accelerated adventitial macrophage infiltration and vasa vasorum proliferation. It was revealed greater macrophage infiltration in CRPTG adipose tissue than in WT adipose tissue and CRP significantly increased the adhesion rate of monocytes through receptor Fcγ RI. Proteome profiling showed CRP over-expression promoted the expression of chemokine (C-X-C motif) ligand 7 (CXCL7) in adipose tissue, transwell assay showed CRP increased monocyte migration indirectly via the induction of CXCL7 expression in adipocytes.ConclusionCRP derived from PVAT was significantly increased in HFD mice and promoted neointimal hyperplasia after vascular injury.

Highlights

Obesity is a major risk factor for cardiovascular diseases and the incidence has risen substantially nowadays [1]
C-reactive protein (CRP) is a frequently used marker of systemic inflammation, the latest landmark CANTOS trial showed those with CRP concentrations less than 2 mg/L achieved by canakinumab treatment had a 25% reduction of major adverse cardiovascular events, which indicated the prognostic value of CRP in primary and secondary prevention of cardiovascular diseases [12]. and elevation of the preprocedural CRP level in patients undergoing percutaneous coronary intervention) (PCI) was shown to be associated with the incidence of adverse cardiac events, such as: in-stent restenosis, especially for whose with obesity and diabetes [13,14,15,16,17]
Overexpression CRP in perivascular adipose tissue (PVAT) promoted neointimal hyperplasia after vascular injury The transplanted WT PVAT and transgenic CRP-expressing (CRPTG) PVAT have the same survival rates in WT mice (75% vs. 75%)

Summary

Introduction

Obesity is a major risk factor for cardiovascular diseases and the incidence has risen substantially nowadays [1]. Without fascia separating PVAT from the intima-media, the interplay between the arterial wall and its PVAT is bidirectional, vascular inflammation affects the pathophysiology of PVAT through paracrine signals, and cytokines produced by adipocytes can permeate freely through the adventitia to the intima, and attract immune cells from peripheral blood to the damaged intima, contributing to the pathogenesis of vascular disease [8, 9]. Elevation of the preprocedural CRP level in patients undergoing PCI was shown to be associated with the incidence of adverse cardiac events, such as: in-stent restenosis, especially for whose with obesity and diabetes [13,14,15,16,17]. Little attention has been paid to the role of CRP produced in the adventitia and PVAT in response to injury, and whether CRP secreted by PVAT promotes neointima formation after vascular injury had not been determined

Methods

Results

Conclusion