title: VEGF-C/VEGFR-3 pathway promotes myocyte hypertrophy and survival in the infarcted myocardium.
abstract: BACKGROUND
  Numerous studies have shown that in addition to angio/lymphangiogenesis, the VEGF family is involved in other cellular actions. We have recently reported that enhanced VEGF-C and VEGFR-3 in the infarcted rat myocardium, suggesting the paracrine/autocrine function of VEGF-C on cardiac remodeling. The current study was designed to test the hypothesis that VEGF-C regulates cardiomyocyte growth and survival in the infarcted myocardium.
  
  
  RESULTS
  Gene profiling and VEGFR-3 expression of cardiomyocytes were assessed by laser capture microdissection/microarray and immunohistochemistry in the normal and infarcted myocardium. The effect of VEGF-C on myocyte hypertrophy and apoptosis during normoxia and hypoxia was detected by RT-PCR and western blotting in cultured rat neonatal cardiomyocytes. VEGFR-3 was minimally expressed in cardiomyocytes of the normal and noninfarcted myocardium, while markedly elevated in the surviving cardiomyocytes of the infarcted myocardium and border zone. Genes altered in the surviving cardiomyocytes were associated with the networks regulating cellular growth and survival. VEGF-C significantly increased the expression of atrial natriuretic factor (ANP), brain natriuretic factor (BNP), and β-myosin heavy chain (MHC), markers of hypertrophy, in neonatal cardiomyocytes. Hypoxia caused neonatal cardiomyocyte atrophy, which was prevented by VEGF-C treatment. Hypoxia significantly enhanced apoptotic mediators, including cleaved caspase 3, 8, and 9, and Bax in neonatal cardiomyocytes, which were abolished by VEGF-C treatment.
  
  
  CONCLUSIONS
  Our findings indicate that VEGF-C/VEGFR-3 pathway exerts a beneficial role in the infarcted myocardium by promoting compensatory cardiomyocyte hypertrophy and survival.
authors.affiliation: Division of Cardiovascular Diseases, Department of Medicine, University of Tennessee Health Science Center Memphis, TN 38163, USA.
authors.forename: Tieqiang
authors.initials: T
authors.lastname: Zhao
authors.affiliation: Division of Cardiovascular Diseases, Department of Medicine, University of Tennessee Health Science Center Memphis, TN 38163, USA.
authors.forename: Wenyuan
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Division of Cardiovascular Diseases, Department of Medicine, University of Tennessee Health Science Center Memphis, TN 38163, USA.
authors.forename: Weixin
authors.initials: W
authors.lastname: Meng
authors.affiliation: Division of Cardiovascular Diseases, Department of Medicine, University of Tennessee Health Science Center Memphis, TN 38163, USA.
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
authors.affiliation: Division of Cardiovascular Diseases, Department of Medicine, University of Tennessee Health Science Center Memphis, TN 38163, USA.
authors.forename: Yuanjian
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Division of Endocrinology, Department of Medicine, University of Tennessee Health Science Center Memphis, TN 38163, USA.
authors.forename: Ivan C
authors.initials: IC
authors.lastname: Gerling
authors.affiliation: Division of Cardiovascular Diseases, Department of Medicine, University of Tennessee Health Science Center Memphis, TN 38163, USA.
authors.forename: Karl T
authors.initials: KT
authors.lastname: Weber
authors.affiliation: Division of Cardiovascular Diseases, Department of Medicine, University of Tennessee Health Science Center Memphis, TN 38163, USA.
authors.forename: Syamal K
authors.initials: SK
authors.lastname: Bhattacharya
authors.affiliation: Division of Cardiovascular Diseases, Department of Medicine, University of Tennessee Health Science Center Memphis, TN 38163, USA.
authors.forename: Rahul
authors.initials: R
authors.lastname: Kumar
authors.affiliation: Division of Cardiovascular Diseases, Department of Medicine, University of Tennessee Health Science Center Memphis, TN 38163, USA.
authors.forename: Yao
authors.initials: Y
authors.lastname: Sun
keywords: VEGF-C; apoptosis; cardiomyocytes; hypertrophy; myocardial infarction