title: Myocardial hypertrophy in the absence of external stimuli is induced by angiogenesis in mice.
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.
authors.affiliation: Angiogenesis Research Center, Section of Cardiology, Department of Medicine, Dartmouth Medical School, Hanover, New Hampshire 03756, USA.
authors.forename: Daniela
authors.initials: D
authors.lastname: Tirziu
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Chorianopoulos
authors.forename: Karen L
authors.initials: KL
authors.lastname: Moodie
authors.forename: Robert T
authors.initials: RT
authors.lastname: Palac
authors.forename: Zhen W
authors.initials: ZW
authors.lastname: Zhuang
authors.forename: Marc
authors.initials: M
authors.lastname: Tjwa
authors.forename: Carmen
authors.initials: C
authors.lastname: Roncal
authors.forename: Ulf
authors.initials: U
authors.lastname: Eriksson
authors.forename: Qiangwei
authors.initials: Q
authors.lastname: Fu
authors.forename: Arye
authors.initials: A
authors.lastname: Elfenbein
authors.forename: Amy E
authors.initials: AE
authors.lastname: Hall
authors.forename: Peter
authors.initials: P
authors.lastname: Carmeliet
authors.forename: Lieve
authors.initials: L
authors.lastname: Moons
authors.forename: Michael
authors.initials: M
authors.lastname: Simons
mesh_terms: D042501:Angiogenic Proteins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D006332:Cardiomegaly / Q000473:pathology / Q000503:physiopathology; D002478:Cells, Cultured; D004452:Echocardiography; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000378:metabolism; D006321:Heart / Q000033:anatomy & histology; D006439:Hemodynamics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000378:metabolism; D018919:Neovascularization, Physiologic; D009929:Organ Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D019076:Transgenes
chemical_list: D042501:Angiogenic Proteins; D004791:Enzyme Inhibitors; D019331:NG-Nitroarginine Methyl Ester