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人血浆和心外膜脂肪组织中C1q/TNF相关蛋白-1水平与充血性心力衰竭的关联

Association Between C1q/TNF-Related Protein-1 Levels in Human Plasma and Epicardial Adipose Tissues and Congestive Heart Failure.

作者信息

Yang Ying, Liu Si, Zhang Rong-Yi, Luo Hui, Chen Ling, He Wen-Feng, Lei Rong, Liu Mu-Rong, Hu Hou-Xiang, Chen Mao

机构信息

Department of Cardiology, West China Hospital, Sichuan University, Chengdu, China.

Department of Cardiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China.

出版信息

Cell Physiol Biochem. 2017;42(5):2130-2143. doi: 10.1159/000479915. Epub 2017 Aug 15.

Abstract

BACKGROUND/AIMS: C1q and tumour necrosis factor-related protein 1 (CTRP1) possesses anti-atherogenic and anti-inflammatory effects. This study investigated whether the CTRP1 levels in the plasma and epicardial adipose tissue (EAT) were associated with congestive heart failure (CHF) and to disclose possible molecular mechanisms.

METHODS

Plasma and tissue samples were obtained from subjects with or without CHF. Plasma levels of CTRP1 were measured by ELISA. The mRNA levels of CTRP1 and inflammatory cytokines were detected by RT-PCR. The protein levels of CTRP1, aldosterone synthase (CYP11B2) and mitogen-activated protein kinase were examined by Western blotting.

RESULTS

The levels of CTRP1 in the plasma and EAT were higher in the CHF patients than those in the controls. There were no differences in the CTRP1 levels in cardiomyocytes between the CHF group and the non-CHF group. An exploratory survival analysis showed that higher CTRP1 values at admission were associated with a worse prognosis after discharge. CTRP1 increased the IL-6 mRNA level in H295R cells. CTRP1 recruited ERK1/2 and Jak-2 for aldosterone release by modulating the CYP11B2 protein level, and brain natriuretic peptide repressed the CTRP1-induced aldosterone release through the JAK2-STAT3 signalling pathways.

CONCLUSION

The CTRP1 levels in the plasma and EAT were increased in the CHF patients. CTRP1 is involved in the pathogenesis of CHF by modulating IL-6 levels and aldosterone release.

摘要

背景/目的:C1q和肿瘤坏死因子相关蛋白1(CTRP1)具有抗动脉粥样硬化和抗炎作用。本研究调查血浆和心外膜脂肪组织(EAT)中的CTRP1水平是否与充血性心力衰竭(CHF)相关,并揭示可能的分子机制。

方法

从有或无CHF的受试者获取血浆和组织样本。采用酶联免疫吸附测定法(ELISA)检测血浆CTRP1水平。通过逆转录-聚合酶链反应(RT-PCR)检测CTRP1和炎性细胞因子的mRNA水平。采用蛋白质印迹法检测CTRP1、醛固酮合酶(CYP11B2)和丝裂原活化蛋白激酶的蛋白水平。

结果

CHF患者血浆和EAT中的CTRP1水平高于对照组。CHF组和非CHF组心肌细胞中的CTRP1水平无差异。一项探索性生存分析显示,入院时较高的CTRP1值与出院后较差的预后相关。CTRP1增加了H295R细胞中白细胞介素-6(IL-6)的mRNA水平。CTRP1通过调节CYP11B2蛋白水平募集细胞外信号调节激酶1/2(ERK1/2)和Janus激酶2(Jak-2)以促进醛固酮释放,而脑钠肽通过JAK2-信号转导和转录激活因子3(STAT3)信号通路抑制CTRP1诱导的醛固酮释放。

结论

CHF患者血浆和EAT中的CTRP1水平升高。CTRP1通过调节IL-6水平和醛固酮释放参与CHF的发病机制。

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