The involvement of vimentin in copper-induced regression of cardiomyocyte hypertrophy

Abstract

Dietary copper supplementation reverses the pressure overload-induced cardiac hypertrophy. Activation of vascular endothelial growth factor receptor-1 (VEGFR-1) and cyclic guanosine monophosphate (cGMP)-dependent protein kinase-1 (PKG-1) is required for the regression. The present study was undertaken to determine the link between VEGFR-1 and PKG-1 in copper regression of cardiomyocyte hypertrophy. Human cardiac myocytes (HCM) or primary cultures of neonatal rat cardiomyocytes were exposed to phenylephrine (PE) at a final concentration of 100 μM for 48 h to induce cell hypertrophy. Copper sulfite was added to cultures of hypertrophic cardiomyocytes at a final concentration of 5 μM elemental copper and incubated for 24 h to reverse cell hypertrophy. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis identified a 56 kDa copper-binding protein, vimentin, which was co-immunoprecipitated with VEGFR-1 and PKG-1. Copper supplementation increased vimentin levels and enhanced PKG-1 activity. Gene silencing using siRNA targeting vimentin prevented copper-induced elevation of vimentin, depressed the activity of PKG-1, and blocked the copper-induced regression of cardiomyocyte hypertrophy. This study demonstrates that vimentin is critically involved in the VEGFR-1 mediated activation of the PKG-1 signaling pathway, leading to regression of cardiomyocyte hypertrophy.

The association of depressed angiogenic factors with reduced capillary density in the Rhesus monkey model of myocardial ischemia

“…Primary cardiomyocytes were isolated from 1 to 3 day-old SPFgrade Sprague-Dawley neonatal rats (DaShuo, CN) and cultured according to a procedure published previously, 16 with some modifications. Upon isolation, cells were maintained at 37 1C in L-DMEM (GIBCO, USA) supplemented with 10% fetal bovine serum (FBS, Hyclone, USA) and 1% penicillin/streptomycin (GIBCO, USA) in a 5% CO 2 incubator.…”

Phosphoproteomic Analysis Reveals Downstream PKA Effectors of AKAP Cypher/ZASP in the Pathogenesis of Dilated Cardiomyopathy

“…Vimentin is commonly recognised as a marker of activated myofibroblasts involved in cardiomyopathy ( 30 ), and several studies have uncovered its cardioprotective effects in cardiomyocytes ( 31 , 32 ). Vimentin and its phosphorylation deserve further exploration.…”

“…Vimentin, a type III intermediate filament protein, is widely distributed in most cells ( 30 ) and has been reported to have a cardioprotective effect in cardiomyocytes ( 31 , 32 ). Vimentin filament assembly and maturation are modified by phosphorylation at Ser72 ( 52 , 53 ).…”