Title: Myocardial hypertrophy in the absence of external stimuli is induced by angiogenesis in mice
Authors: Tirziu, Daniela
Chorianopoulos, Emmanuel
Moodie, Karen L
Palac, Robert T
Zhuang, Zhen W
Tjwa, Marc
Roncal Mancho, Carmen
Eriksson, Ulf
Fu, Qiangwei
Elfenbein, Arye
Hall, Amy E
Carmeliet, Peter
Moons, Lieve
Simons, Michael # ×
Issue Date: Nov-2007
Series Title: Journal of Clinical Investigation vol:117 issue:11 pages:3188-97
Abstract: Although studies have suggested a role for angiogenesis in determining heart size during conditions demanding enhanced cardiac performance, the role of EC mass in determining the normal organ size is poorly understood. To explore the relationship between cardiac vasculature and normal heart size, we generated a transgenic mouse with a regulatable expression of the secreted angiogenic growth factor PR39 in cardiomyocytes. A significant change in adult mouse EC mass was apparent by 3 weeks following PR39 induction. Heart weight; cardiomyocyte size; vascular density normalization; upregulation of hypertrophy markers including atrial natriuretic factor, beta-MHC, and GATA4; and activation of the Akt and MAP kinase pathways were observed at 6 weeks post-induction. Treatment of PR39-induced mice with the eNOS inhibitor L-NAME in the last 3 weeks of a 6-week stimulation period resulted in a significant suppression of heart growth and a reduction in hypertrophic marker expression. Injection of PR39 or another angiogenic growth factor, VEGF-B, into murine hearts during myocardial infarction led to induction of myocardial hypertrophy and restoration of myocardial function. Thus stimulation of vascular growth in normal adult mouse hearts leads to an increase in cardiac mass.
ISSN: 0021-9738
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Animal Physiology and Neurobiology Section - miscellaneous
Vesalius Research Centre (-)
Molecular and Vascular Biology
Laboratory of Angiogenesis and Vascular Metabolism (Vesalius Research Center) (+)
× corresponding author
# (joint) last author

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