Nitric oxide mediates the mitogenic effect of vegf on coronary
venular endothelium.
Morbidelli, Lucia, Chung-Ho Chang, Janice G. Douglas, Harris J.
Granger, Fabrizio Ledda, and Marina Ziche.
Department of Preclinical and Clinical Pharmacology, University of
Florence, Florence, Italy; Division of Hypertension, School of
Medicine, Case Western Reserve University, Cleveland, OH, USA; and
Microcirculation Research Institute and Department of Medical
Physiology, Texas A&M University, College Station, TX, USA.
APStracts 2:0493H, 1995.
Vascular endothelial growth factor (VEGF) is a secreted protein that
is a specific growth factor for endothelial cells. We have recently
demonstrated that nitric oxide (NO)-donors and vasoactive peptides
promoting NO-mediated vasorelaxation induce angiogenesis in vivo as
well as endothelial cell growth and motility in vitro; in contrast,
inhibitors of NO synthase suppress angiogenesis. In this study we
have investigated the role of NO in mediating the mitogenic effect of
VEGF on cultured microvascular endothelium isolated from coronary
post-capillary venules. VEGF induced a dose-dependent increase in
cell proliferation and DNA synthesis. The role of NO was determined
by monitoring proliferation or cyclic GMP levels in the presence and
absence of NO synthase blockers. The proliferative effect evoked by
VEGF was reduced by pre-treatment of the cells with NO synthase
inhibitors. Exposure of the cells to VEGF induced a significant
increment in cyclic GMP levels. This effect was potentiated by
Superoxide dismutase (SOD) addition and was abolished by NO synthase
inhibitors. VEGF stimulates proliferation of post-capillary
endothelial cells through the production of NO and cyclic GMP
accumulation.
Received 11 August 1995; accepted in final form 23 October 1995.
APS Manuscript Number H758-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 30 November 95