PINCH1 knockout aggravates myocardial infarction in mice via mediating the NF‑κB signaling pathway

Wang,Xuejun; Su,Jinwen; Lin,Zhikang; Liu,Kangyong; Zhuang,Yu

doi:10.3892/etm.2021.10984

PINCH1 knockout aggravates myocardial infarction in mice via mediating the NF‑κB signaling pathway

Authors:
- Xuejun Wang
- Jinwen Su
- Zhikang Lin
- Kangyong Liu
- Yu Zhuang
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Affiliations: Department of Cardiology, Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital, Shanghai 201318, P.R. China, Department of Cardiology, Shanghai Ninth People's Hospital Affiliated to Shanghai JiaoTong University School of Medicine, Shanghai 200011, P.R. China, Department of Neurology, Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital, Shanghai 201318, P.R. China, Department of Cardiovascular Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, P.R. China
Published online on: November 22, 2021 https://doi.org/10.3892/etm.2021.10984
Article Number: 62
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Myocardial infarction (MI), the leading cause of death among patients with cardiovascular diseases, is characterized by acute cardiac muscle injury due to severe impairment of the coronary blood supply, which may lead to cardiogenic shock and cardiac arrest. Particularly interesting new cysteine histidine rich 1 (PINCH1) protein, a key component of the integrin signaling pathway, interacts with several proteins and serves a vital role in numerous cellular processes, including cytoskeleton remodeling, cell proliferation and cell migration. To investigate the role of PINCH1 in heart injury in the present study, PINCH1 was knocked out in the myocardial tissue of mice (age, 18 weeks) to induce MI. In addition, cell viability, migration and apoptosis, as well as the expression levels of NF‑κB‑associated proteins were determined in murine HL1 cardiomyocytes with a conditional PINCH1 shRNA using Cell Counting Kit‑8, Transwell, flow cytometry and western blot assays, respectively. Furthermore, the cardiac expansion and myocardial fibrosis in PINCH1 knockout mice was investigated in vivo by performing morphological and histological examinations. Additionally, the murine ventricular myocardial ultrastructure was evaluated using an electron microscope, and the cardiomyocyte apoptotic rate and expression levels of NF‑κB‑related proteins were determined using TUNEL and western blot assays, respectively. The results showed that the apoptotic rate in the in vivo PINCH1 knockdown group was significantly increased. In addition, the protein expression levels of NF‑κB signaling pathway‑related proteins, including NF‑κB, myeloid differentiation factor 88, TNF‑α and caspase‑3, were significantly increased in the in vivo PINCH1 knockdown group compared with the wild‑type group, but the protein expression of MMP2 and MMP9 were the opposite. Overall, the in vitro and in vivo results revealed that PINCH1 knockout in mice significantly aggravated MI via the NF‑κB signaling pathway.

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