title: Brief Communication: Copper suppression of vascular endothelial growth factor receptor-2 is involved in the regression of cardiomyocyte hypertrophy.
abstract: Previous studies revealed that copper (Cu)-induced regression of cardiomyocyte hypertrophy is associated with enhanced activity in the vascular endothelial growth factor receptor-1 (VEGFR-1) signaling pathway. The mechanism by which Cu enhances the activity of VEGFR-1 pathway remains to be defined. The present study was undertaken to test the hypothesis that Cu enhances the VEGFR-1 signaling pathway via suppression of the VEGFR-2 signaling pathway. Primary cultures of neonatal rat cardiomyocytes were exposed to phenylephrine (PE) at a final concentration of 100 µM in cultures for 48 h to induce cell hypertrophy. The hypertrophic cardiomyocytes were exposed to copper sulfate at a final concentration of 5 µM Cu in cultures for 24 h. Western blot analysis showed that PE increased the protein levels of both VEGFR-1 and VEGFR-2. Cu supplementation significantly reduced the increase in VEGFR-2, but had no effect on the elevation of VEGFR-1. Real-time polymerase chain reaction analysis found no difference in the mRNA levels between the VEGFR-1 and VEGFR-2 under the conditions defined above. This study thus demonstrated that Cu selectively suppressed PE-elevated VEGFR-2 levels likely via post-translational regulation, leading to the VEGFR-1 signaling pathway becoming dominant and thereby regressing cardiomyocyte hypertrophy.
authors.affiliation: Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.affiliation: Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Lin
authors.affiliation: Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Sun
authors.affiliation: Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China yjkang01@louisville.edu.
authors.forename: Y James
authors.initials: YJ
authors.lastname: Kang
keywords: Copper; VEGF; VEGFR-1; VEGFR-2; cardiomyocyte; hypertrophy