Mechanistic insights into copper-induced regression of heart hypertrophy.

Copper;VEGFR;Vimentin;Hypertrophy;VEGF;Heart failure

Katherine Bourcy

University:University of Louisville

Department:Pharmacology and Toxicology

关键词: Copper;    VEGFR;    Vimentin;    Hypertrophy;    VEGF;    Heart failure;   

Others  :  https://ir.library.louisville.edu/cgi/viewcontent.cgi?article=1132&context=etd

美国|英语

来源: The Universite of Louisville's Institutional Repository

【 摘 要 】

Previous studies have shown that copper (Cu) supplementation at physiologically relevant levels reverses cardiac myocyte hypertrophy induced by phenylephrine (PE), and that this effect was VEGF-dependent. Yet, the amount of VEGF in the media was unchanged. However, we observed that Cu caused an increase in the ratio of VEGFR-1:VEGFR-2 as well as an increase in PKG-1 activity. PKG-1 activity is associated with the regression of cardiac myocyte hypertrophy. The present study was undertaken to test the hypothesis that VEGFR-1 is associated with PKG-1 and their association is involved in Cu induced regression of cardiomyocyte hypertrophy. Human cardiac myocytes (HCM) in cultures were exposed to phenylephrine (PE) at a final concentration of 100 µM for 48 hours to induce cell hypertrophy. Copper sulfate at a final concentration of 5 µM was added to the hypertrophic HCM cultures for 24 hours with the concomitant presence of PE to reverse the hypertrophy. Both hypertrophic and hypertrophic-reversed HCM cells underwent immunoprecipitation using anti-VEGFR-1 antibody or anti-PKG-1 antibody. The immune complex underwent gel-electrophoresis separation and Western blotting and LC-MSIMS analysis. Proteomic analysis identified Vimentin in the immune complexes that immunoprecipitated with VEGFR-1 and PKG-1. This study thus demonstrates that the association between VEGFR-1 with PKG-1 is mediated by Vimentin, and that Vimentin plays a critical role in copper regression of cardiac myocyte hypertrophy.