Formation of a f2-isoprostane, 8-epi-pgf2, in vascular smooth
muscle cells by elevated glucose and growth factors.
Natarajan, Rama, Linda Lanting, Noe Gonzales, and Jerry Nadler.
Department of Diabetes, Endocrinology and Metabolism, City of Hope
Medical Center, Duarte, CA 91010
APStracts 2:0559H, 1995.
Recently a series of non-cyclooxygenase-derived prostanoids were
identified in vivo in humans and in animal models of free radical
injury as products of free radical-catalyzed peroxidation of
arachidonic acid. One of these, a F2-isoprostane, 8-epi-prostaglandin
F2[alpha] (8-epi-PGF2[alpha]), is a potent renal vasoconstrictor and
can increase vascular smooth muscle cell (VSMC) DNA synthesis. In the
present study we have evaluated whether F2-isoprostanes play a role
in diabetic vascular dysfunction by studying the formation of 8-epi
-PGF2[alpha] in porcine VSMC cultured under hyperglycemic conditions.
8-epi-PGF2[alpha] levels were quantitated by a specific enzyme
immunoassay. We also examined whether certain VSMC growth factors
such as angiotensin II, platelet-derived growth factor and
transforming growth factor-[beta] could also regulate the formation
of 8-epi-PGF2[alpha]. We observed that porcine VSMC cultured under
high glucose conditions produced significantly higher amounts of 8
-epi-PGF2[alpha] compared to normal glucose (3.7 +/- 0.13 ng/106 cells
high glucose vs 2.9 +/- 0.2 ng in normal glucose, p< 0.05).
Furthermore, all the three growth factors tested evoked significant
dose- dependent formation of 8-epi-PGF2[alpha] (ranging from 125-220
% of control). These results suggest that 8-epi-PGF2[alpha] formation
as a result of hyperglycemia or due to growth factor action may lead
to increased VSMC growth and contribute to the complications of
diabetes and cardiovascular disease.
Received 11 October 1994; accepted in final form 4 December 1995.
APS Manuscript Number H906-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 23 December 95