C-reactive protein derived from perivascular adipose tissue accelerates injury-induced neointimal hyperplasia
C-reactive protein derived from perivascular adipose tissue accelerates injury-induced neointimal hyperplasia
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源自血管周围脂肪组织的 C 反应蛋白加速损伤引起的内膜增生
DOI：
10.1186/s12967-020-02226-x
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发表时间：
2020-02-11
影响因子：
7.4
通讯作者：
Chen, Yang-Xin
中科院分区：
文献类型：
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作者：
Chen, Jia-Yuan;Zhu, Xiao-Lin;Chen, Yang-Xin
目的肥胖患者血管周围脂肪组织（PVAT）炎症在心血管疾病中起重要作用。肥胖患者c反应蛋白（CRP）水平显著升高，并与心血管疾病的发生和进展相关。我们验证了来自肥胖患者PVAT的CRP有助于损伤后血管重构的假设。方法高脂饮食（HFD）显著增加PVAT中CRP的表达。我们将野生型（WT）或转基因crp表达型（CRPTG）小鼠的胸主动脉PVAT移植到WT小鼠损伤的股动脉中。结果在股动脉损伤后4周，接受CRPTG小鼠PVAT的WT小鼠与接受WT PVAT的WT小鼠相比，新内膜/中膜比例显著增加。移植的CRPTG - PVAT也显著加速了血管外巨噬细胞的浸润和血管的增殖。结果显示，CRPTG脂肪组织中巨噬细胞的浸润量大于WT脂肪组织，CRP通过受体Fc γ RI显著增加单核细胞的黏附率。蛋白质组学分析显示，CRP过表达可促进脂肪组织中趋化因子（C-X-C基序）配体7 （CXCL7）的表达，transwell实验显示，CRP通过诱导脂肪细胞中CXCL7的表达间接增加单核细胞迁移。结论PVAT衍生的CRP在HFD小鼠血管损伤后显著升高，促进血管内膜增生。
Aim Inflammation 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. Methods A 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. Results At 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 Fc gamma 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. Conclusion CRP derived from PVAT was significantly increased in HFD mice and promoted neointimal hyperplasia after vascular injury.