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血管相关平滑肌细胞蛋白聚糖基因敲除通过下调非胶原纤维和促进炎症反应诱导小鼠心肌纤维化。

VASN knockout induces myocardial fibrosis in mice by downregulating non-collagen fibers and promoting inflammation.

作者信息

Sun Junming, Yin Siwei, Li Qiurui, Zhang Jun, Guo Xiaoping, Yu Na, Hu Bing, Ouyang Yiqiang, Huang Qiaojuan, He Min

机构信息

Laboratory Animal Center, Guangxi Medical University, Nanning, Guangxi, China.

Department of Cardiology, The Second Affiliated Hospital, Guangxi Medical University, Nanning, Guangxi, China.

出版信息

Front Pharmacol. 2025 Jan 17;15:1500617. doi: 10.3389/fphar.2024.1500617. eCollection 2024.

Abstract

Myocardial fibrosis (MF) is an important cause of heart failure and cardiac arrest. Vasorin knockout (VASN) leads to pathological cardiac hypertrophy (PCH); however, it is not yet clear whether this PCH transitions to MF in mice. VASN-knockout mice showed typical pathological, imaging, and molecular features of MF upon hematoxylin and eosin staining, Masson staining, Sirius red staining, quantitative polymerase chain reaction (qPCR), immunohistochemistry-paraffin (IHC-P), and immunofluorescence analyses. RNA was extracted from mouse heart tissue, identified, and sequenced . Differential analysis of the genes showed that the extracellular matrix (ECM) genes (, and ) had strong correlations while their expression levels were significantly reduced by qPCR, IHC-P, and Western blotting. The expression levels of the ECM genes were significantly reduced but those of the inflammatory factors (IL1β and IL6) were significantly upregulated in the heart tissues of VASN-knockout mice. These preliminary results reveal that VASN knockout induces MF by regulating the non-collagen fibers and inflammation.

摘要

心肌纤维化(MF)是心力衰竭和心脏骤停的重要原因。血管紧张素原敲除(VASN)会导致病理性心脏肥大(PCH);然而,在小鼠中这种PCH是否会转变为MF尚不清楚。苏木精-伊红染色、Masson染色、天狼星红染色、定量聚合酶链反应(qPCR)、免疫组织化学-石蜡(IHC-P)和免疫荧光分析显示,VASN基因敲除小鼠呈现出MF典型的病理、影像学和分子特征。从小鼠心脏组织中提取RNA,进行鉴定和测序。基因差异分析表明,细胞外基质(ECM)基因(、和)具有很强的相关性,而通过qPCR、IHC-P和蛋白质免疫印迹法检测发现它们的表达水平显著降低。在VASN基因敲除小鼠的心脏组织中,ECM基因的表达水平显著降低,但炎症因子(IL1β和IL6)的表达水平显著上调。这些初步结果表明,VASN基因敲除通过调节非胶原纤维和炎症反应诱导MF的发生。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4359/11782114/24da742224e7/fphar-15-1500617-g001.jpg

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