Proliferation and migration of endothelial cells is promoted by
endothelins via activation of etb receptors.
Morbidelli, Lucia, Claudio Orlando, Carlo A. Maggi, Fabrizio Ledda,
and Marina Ziche.
Department of Preclinical and Clinical Pharmacology "Mario
Aiazzi Mancini" Clinical Biochemistry Unit, Department of
Clinical Physiopathology, University of Florence, 50134 Florence; and
Pharmacology Department A. Menarini Pharmaceuticals, 50131 Florence,
Italy
APStracts 2:0101H, 1995.
The growth and migration of endothelial cells are the prerequisites
for vascular remodelling. The effects of endothelin 1 and 3 (ET-1,
ET-3) on the proliferation and migration of endothelial cells
isolated from bovine adrenal capillaries (BACE) and human umbilical
veins (HUVEC) have been investigated. Cell proliferation (measured as
DNA synthesis and as total cell number) and migration were
significantly increased by ET-1 and ET-3. Dose dependent
proliferation was produced by ET-1 and ET-3 in both cell lines, with
maximal effects at 0.1 nM concentration. ET-1 and ET-3 also
stimulated BACE and HUVEC mobilization in a dose-dependent manner.
The maximal responses were obtained at 10 nM concentration in both
BACE and HUVEC. The full agonist for the ETB receptor, ET(16-21), was
able to reproduce the effects of endothelin on proliferation and
migration of both cell lines. Modification of ET(16-21) at Leu17 and
Ile19 and amidation of the COOH terminal were accompanied by loss of
activity. The ETB receptor antagonist IRL 1038 blocked the migration
induced by ET-3 and ET(16-21), while the ETA receptor antagonist BQ
123 was not effective. We conclude that endothelins, by favouring
endothelial cell growth and mobilization, can contribute to
neovascularization through an autocrine mechanism which requires ETB
receptor activation.
Received 4 November 1994; accepted in final form 14 March 1995.
APS Manuscript Number H987-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 4 April 1995.