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Evaluation of Angiogenic Activity in the Heart Using Isolated Primary Adult Cardiomyocyte Model
Author(s) -
Konorev Eugene A,
Leychenko Anna,
Collier Eric,
Matter Michelle,
Kalyanaraman B
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.754.6
Subject(s) - hypoxia (environmental) , downregulation and upregulation , angiogenesis , vascular endothelial growth factor a , vascular endothelial growth factor , endocrinology , medicine , myocyte , muscle hypertrophy , chemistry , vegf receptors , microbiology and biotechnology , biology , gene , biochemistry , oxygen , organic chemistry
Cardiac pressure and volume overload is a potent stimulus for cardiac hypertrophy. The adaptive value of hypertrophic remodeling is largely determined by the ability of the heart to develop new vasculature, to accommodate the growth of myocardial tissue. This study focused on the production of proangiogenic vascular endothelial growth factor (VEGF) by cardiomyocytes. We cultured primary adult rat cardiomyocytes (ARCM) under hypoxic conditions, and collected culture media for VEGF measurements. Hypoxia caused a 3‐fold increase in VEGF release from ARCM. Primary adult mouse cardiomyocytes (AMCM) responded to hypoxia in a similar way. Hypoxia upregulated the expression of genes in AMCM that are controlled by hypoxia‐response elements. Expression of vegfa increased 5 to 8‐fold in hypoxic AMCM. Cobalt chloride, an agent that induces hypoxia‐like response, increased both VEGF production and vegfa expression in these cells. In separate experiments, mechanical stretch of ARCM caused a 3‐fold increase in VEGF release, as compared to non‐stretched cells. Thus, we conclude that cultured primary cardiomyocytes respond to hypoxia and mechanical stretch, factors that are present in overloaded hearts, with a significantly upregulated release of VEGF. The study suggests that the model may be valuable in designing agents that regulate the production of angiogenic factors by cardiomyocytes in the heart.