Cardiology

The MEK/ERK Module Is Reprogrammed in Remodeling Adult Cardiomyocytes.




Related Articles

The MEK/ERK Module Is Reprogrammed in Remodeling Adult Cardiomyocytes.

Int J Mol Sci. 2020 Sep 01;21(17):

Authors: Thomas K, Ayse C, Natalia K, Peter B, Bedriye SH, Praveen G, Hakan A, Markus S, Wolfgang S, Yeong-Hoon C, Miroslav B, Manfred R

Abstract
Fetal and hypertrophic remodeling are hallmarks of cardiac restructuring leading chronically to heart failure. Since the Ras/Raf/MEK/ERK cascade (MAPK) is involved in the development of heart failure, we hypothesized, first, that fetal remodeling is different from hypertrophy and, second, that remodeling of the MAPK occurs. To test our hypothesis, we analyzed models of cultured adult rat cardiomyocytes as well as investigated myocytes in the failing human myocardium by western blot and confocal microscopy. Fetal remodeling was induced through endothelial morphogens and monitored by the reexpression of Acta2, Actn1, and Actb. Serum-induced hypertrophy was determined by increased surface size and protein content of cardiomyocytes. Serum and morphogens caused reprogramming of Ras/Raf/MEK/ERK. In both models H-Ras, N-Ras, Rap2, B- and C-Raf, MEK1/2 as well as ERK1/2 increased while K-Ras was downregulated. Atrophy, MAPK-dependent ischemic resistance, loss of A-Raf, and reexpression of Rap1 and Erk3 highlighted fetal remodeling, while A-Raf accumulation marked hypertrophy. The knock-down of B-Raf by siRNA reduced MAPK activation and fetal reprogramming. In conclusion, we demonstrate that fetal and hypertrophic remodeling are independent processes and involve reprogramming of the MAPK.

PMID: 32882982 [PubMed - in process]

Source link







Related posts

Hemodynamic Response in Low-Flow Low-Gradient Aortic Stenosis With Preserved Ejection Fraction After TAVR

Newsemia

Want to Know More About Your Health Condition? Take One of Our Classes!

Newsemia

Proportionate or disproportionate secondary mitral regurgitation: how to untangle the Gordian knot?

Newsemia

This website uses cookies to improve your experience. We'll assume you're ok with this, but you can opt-out if you wish. Accept Read More

Privacy & Cookies Policy