BackgroundLINC00961 has been implicated in the development of cardiovascular diseases, and its potential mechanisms of action have been suggested. Here, we investigated the role of LINC00961 in the endothelial-mesenchymal transition (EndMT) induced by TGF-β and myocardial fibrosis following myocardial infarction(MI). Methods and ResultsHuman cardiac microvascular endothelial cells (HCMECs) and male wild-type (WT) mice were used. HCMECs were exposed to TGF-β in serum-free medium for 48 h to induce EndMT. CCK8 and Flow cytometry analysis were used to examine cell viability and assess apoptosis. To identify CD31+/α-SMA+ double-positive cells, immunofluorescence staining was used. Western blotting and PCR were used for protein and mRNA analyses. TGF-β time-dependently contributed to EndMT and injuries of HCMECs, LINC00961 attenuated the injury and EndMT caused by TGF-β. WT and LINC00961 knockout C57BL/6 mice were subjected to left anterior descending coronary artery ligation to trigger MI. Myocardial fibrosis was assessed using H&E and Masson's trichrome staining, and Echocardiography was performed to evaluate cardiac function. Western blotting and PCR were used for protein and mRNA expression analyses. MI contributed to myocardial fibrosis and the reduction of cardiac function, LINC00961 and SB-431542 (TGF-β selective inhibitor) attenuated the reduced cardiac function and myocardial fibrosis following MI. ConclusionLINC00961 attenuates EndMT induced by TGF-β and myocardial fibrosis following MI, owing by suppressing the TGF-β pathway, reducing p-SMAD2/3 expression, and inhibiting SNAIL and SLUG.
