Regulatory Mechanism of LINC00152 on Aggravating Heart Failure through Triggering Fibrosis in an Infarcted Myocardium

Abstract

Objective. To elucidate the role of LINC00152 in the progression of heart failure following myocardial infarction. Patients and Methods. Serum levels of LINC00152 in acute myocardial infarction (AMI) patients were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Receiver operating characteristic (ROC) curves were depicted for assessing the diagnostic value of LINC00152 in AMI. Subsequently, an in vivo AMI model was generated in mice. LINC00152 level in a mouse infarcted myocardium was detected. Echocardiogram was conducted to evaluate the influence of LINC00152 on cardiac function in AMI mice. Primary cardiac fibroblasts were isolated from neonatal mice. After knockdown of LINC00152, proliferative and migratory changes in primary cardiac fibroblasts were assessed by cell counting kit-8 (CCK-8) and transwell assay, respectively. The regulatory effect of LINC00152 on Smad7 level was determined by qRT-PCR. Finally, the involvement of Smad7 in LINC00152-regulated proliferative and migratory abilities in primary cardiac fibroblasts was explored by rescue experiments. Results. Serum level of LINC00152 was elevated in AMI patients. ROC curves demonstrated the diagnostic potential of LINC00152 in AMI (95% CI: 0.806-0.940, $p=0.034$ ). In myocardial tissues collected from AMI mice, LINC00152 level was higher than those collected from mice of the sham group. LVEF and FS markedly decreased in AMI mice overexpressing LINC00152 on the 4th week of AMI modeling. After knockdown of LINC00152 in primary cardiac fibroblasts, proliferative and migratory abilities were declined, which were abolished by Smad7 intervention. Conclusions. By downregulating Smad7, LINC00152 aggravates heart failure following AMI via promoting the proliferative and migratory abilities in cardiac fibroblasts.