Host: The Japanese Pharmacological Society
Name : The 97th Annual Meeting of the Japanese Pharmacological Society
Number : 97
Location : [in Japanese]
Date : December 14, 2023 - December 16, 2023
Yes-associated protein 1 (YAP), a transcriptional co-activator, is known to regulate cell growth and organ size. We have shown previously that YAP is activated in response to acute pressure overload (PO), and that YAP cardiac-specific heterozygous knockout (YAPchKO) mice are suppressed adaptive cardiac hypertrophy with inhibition of GLUT1 upregulation during acute PO. Furthermore, we found that YAP promotes glycolysis by upregulating GLUT1 in cultured rat ventricular myocytes. Glycolysis is intimately involved in cell growth. Thus, we examined whether AAV-mediated GLUT1 overexpression rescues adaptive cardiac hypertrophy during acute PO in YAPchKO mice. Wild-type (WT) or YAPchKO mice were injected with AAV-control or AAV-GLUT. After 14 days, these mice were subjected to sham or transverse artic constriction (TAC) for 7 days. TAC induced adaptive cardiac hypertrophy in WT mice injected with both AAVs. In contrast, left ventricular (LV) dysfunction, LV dilation, and inhibition of cardiac hypertrophy were observed in YAPchKO mice injected with AAV-control after TAC. AAV-GLUT1 injection successfully rescued GLUT1 upregulation, LV function, and cardiac hypertrophy in YAPchKO mice after TAC. These results suggest that YAP-induced upregulation of GLUT1 plays a critical role in promoting adaptive cardiac hypertrophy during acute PO.
