title: 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.
authors.affiliation: Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China. yjkang01@louisville.edu.
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.forename: Katherine
authors.initials: K
authors.lastname: Bourcy
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Miao
authors.initials: M
authors.lastname: Sun
authors.forename: Y James
authors.initials: YJ
authors.lastname: Kang
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000378:metabolism*; D002478:Cells, Cultured; D003300:Copper / Q000378:metabolism*; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism*; D006801:Humans; D032383:Myocytes, Cardiac / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism; D014746:Vimentin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*
chemical_list: D014746:Vimentin; D003300:Copper; D040281:Vascular Endothelial Growth Factor Receptor-1; D017869:Cyclic GMP-Dependent Protein Kinases