VEGF-C/VEGFR-3 pathway promotes myocyte hypertrophy and survival in the infarcted myocardium

Tieqiang Zhao, Wenyuan Zhao, Weixin Meng, Chang Liu, Yuanjian Chen, Ivan Gerling, Karl Weber, Syamal Bhattacharya, Rahul Kumar, Yao Sun

Research output: Contribution to journalArticle

13 Citations (Scopus)

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. Methods and 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. Conclusion: Our findings indicate that VEGF-C/VEGFR-3 pathway exerts a beneficial role in the infarcted myocardium by promoting compensatory cardiomyocyte hypertrophy and survival.

Original languageEnglish (US)
Pages (from-to)697-709
Number of pages13
JournalAmerican Journal of Translational Research
Volume7
Issue number4
StatePublished - Jan 1 2015

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Vascular Endothelial Growth Factor Receptor-3
Vascular Endothelial Growth Factor C
Cardiac Myocytes
Muscle Cells
Hypertrophy
Myocardium
Atrial Natriuretic Factor
Rats
Microdissection
Genes
Myosin Heavy Chains
Brain Natriuretic Peptide
Lymphangiogenesis
Laser Capture Microdissection
Microarrays
Caspase 3
Caspase 9
Caspase 8
Vascular Endothelial Growth Factor A
Growth

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Clinical Biochemistry
  • Cancer Research

Cite this

VEGF-C/VEGFR-3 pathway promotes myocyte hypertrophy and survival in the infarcted myocardium. / Zhao, Tieqiang; Zhao, Wenyuan; Meng, Weixin; Liu, Chang; Chen, Yuanjian; Gerling, Ivan; Weber, Karl; Bhattacharya, Syamal; Kumar, Rahul; Sun, Yao.

In: American Journal of Translational Research, Vol. 7, No. 4, 01.01.2015, p. 697-709.

Research output: Contribution to journalArticle

Zhao, Tieqiang ; Zhao, Wenyuan ; Meng, Weixin ; Liu, Chang ; Chen, Yuanjian ; Gerling, Ivan ; Weber, Karl ; Bhattacharya, Syamal ; Kumar, Rahul ; Sun, Yao. / VEGF-C/VEGFR-3 pathway promotes myocyte hypertrophy and survival in the infarcted myocardium. In: American Journal of Translational Research. 2015 ; Vol. 7, No. 4. pp. 697-709.
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