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.

Acute myocardial infarction (AMI) is a form of cardiomyopathy in which a blocked coronary artery leads to an irreversible loss of cardiomyocytes due to inadequate blood and oxygen supply to the distal myocardium tissues, eventually leading to heart failure. Recently, studies have revealed that microRNA (miRNA/miR)-24 has diagnostic value in the pathogenesis of AMI by affecting multiple cell processes such as cell proliferation, differentiation and apoptosis. However, the specific mechanism of miR-24 in ischemia-reperfusion injury (IRI) after AMI remains to be fully elucidated. The present study aimed to investigate the effects and mechanisms of miR-24 in IRI. In vitro , the current study detected cellular apoptosis and apoptotic-related protein expression levels in the cardiomyocyte H9C2 cell line (negative control group, model group and miRNA group) via flow cytometry and western blot analysis. In the in vivo study, rats were randomly divided into sham, model and miRNA groups. The infarct area was observed using nitro blue tetrazolium staining, pathological changes of the myocardium were detected via hematoxylin and eosin staining and TUNEL staining was used to detect cardiomyocyte apoptosis. The expression levels of related proteins were evaluated via immunohistochemistry and western blot analysis. The in vitro and in vivo results demonstrated that miR-24 significantly inhibited cardiomyocyte apoptosis compared with the model group. Concurrently, the expression levels of proteins associated with the NF-κB/TNF-α pathway (NF-κB, caspase-3, Bax, Bcl-2, TNF-α, vascular cell adhesion molecule 1, intercellular adhesion molecule 1 and monocyte chemoattractant protein-1) in the miRNA group were significantly different from the model group (P<0.001). Compared with the model group, miR-24 significantly improved pathological damage and infarct size of rat myocardium. Overall, the present results suggested that miR-24 improves myocardial injury in rats by inhibiting the NF-κB/TNF-α pathway.