High glucose and endothelial cell growth: novel effects independent of autocrine
TGF-ß1 and hyperosmolarity.
McGinn, S., P. Poronnik, M. King, E. D. M. Gallery, and C. A. Pollock.
1Department of Medicine, Kolling Institute: Renal Research Group, and 2Department
of Immunology, Royal North Shore Hospital, St Leonards, New South Wales 2065; and
3Department of Physiology, University of Sydney, New South Wales 2006, Australia
APStracts 10:0059C, 2003.
Human endothelial cells were exposed to 5 mM glucose (control), 25 mM (high) glucose,
or osmotic control for 72 h. TGF-ß1 production, cell growth, death, and cell cycle
progression, and the effects of TGF-ß1 and TGF-ß neutralization on these parameters
were studied. High glucose and hyperosmolarity increased endothelial TGF-ß1 secretion
(P < 0.0001) and bioactivity (P < 0.0001). However, high glucose had a greater effect
on reducing endothelial cell number (P < 0.001) and increasing cellular protein content
(P < 0.001) than the osmotic control. TGF-ß antibody only reversed the
antiproliferative and hypertrophic effects of high glucose. High glucose altered cell cycle
progression and cyclin-dependent kinase inhibitor (CDKI) expression independently of
hyperosmolarity. High glucose increased endothelial cell apoptosis (P < 0.01), whereas
hyperosmolarity induced endothelial cell necrosis (P < 0.001). TGF-ß antibody did not
reverse the apoptotic effects observed with high glucose. Exogenous TGF-ß1 mimicked
the increased S phase delay but not endoreduplication observed with high glucose. High
glucose altered endothelial cell growth, apoptosis, and cell cycle progression. These
growth effects occurred principally via a TGF-ß1 autocrine pathway. In contrast,
apoptosis and endoreduplication occurred independently of this cytokine and
hyperosmolarity.
Received 3 October 2002; accepted in final form 11 January 2003
APS Manuscript Number C466-2.
Article publication pending Am J Physiol Cell Physiol
ISSN 1080-4757 Copyright 2003 The American Physiological Society.
Published in APStracts on 25 March 2003