Extracorporeal shock waves protect cardiomyocytes from doxorubicin-induced cardiomyopathy by upregulating survivin via the integrin-ILK-Akt-Sp1/p53 axis.

摘要: Doxorubicin (DOX) is a widely used anti-cancer drug; however, it has limited application due to cardiotoxicity. Extracorporeal shock waves (ESW) have been suggested treat inflammatory and ischemic diseases, but the concrete effect of ESW in DOX-induced cardiomyopathy remain obscure. After H9c2 cells were subjected (0.04 mJ/cm2), they treated with 1 μM DOX. As result, protected cardiomyocytes from cell death. DOX downregulated p-Akt survivin expression, whereas treatment recovered both, suggesting its anti-apoptotic effect. activated integrin αvβ3 αvβ5, cardiomyocyte mechanosensors, followed by upregulation ILK, levels. Further, Sp1 p53 determined as key transcriptional factors mediating expression via Akt phosphorylation ESW. In vivo acute model, echocardiographic results showed that group cardiomyopathy; left ventricular function was improved. The immunohistochemical staining increased Bcl2 ESW + DOX compared those DOX-injected group. conclusion, non-invasive shockwaves protect upregulating integrin-ILK-Akt-Sp1/p53 pathway. study proposed new kind specific safe therapy against cardiomyopathy.