Patients with diabetes are more prone to developing heart failure in the presence of high blood pressure than those without diabetes. Yes-associated protein (YAP), a key effector of the Hippo signaling pathway, is persistently activated in diabetic hearts, and YAP plays an essential role in mediating the exacerbation of heart failure in response to pressure overload in the hearts of mice fed a high-fat diet. YAP induced dedifferentiation of cardiomyocytes through activation of transcriptional enhancer factor 1 (TEAD1), a transcription factor. Thus, YAP and TEAD1 are promising therapeutic targets for diabetic patients with high blood pressure to prevent the development of heart failure.
Keywords: HF, heart failure; HFD, high-fat diet; Hippo pathway; LV, left ventricular; Lats2, large tumor suppressor kinase 2; Mst1, mammalian sterile 20-like 1; ND, normal diet; OSM, oncostatin M; PO, pressure overload; Runx1, runt-related transcription factor 1; TAC, transverse aortic constriction; TAZ, transcriptional coactivator with PDZ-binding motif; TEAD, transcriptional enhancer factor; YAP, Yes-associated protein; diabetes; diabetic cardiomyopathy; pressure overload.
© 2019 Published by Elsevier on behalf of the American College of Cardiology Foundation.