Diabetic rbc induced oxidant stress leads to pecam-1
phosphorylation and transendothelial migration of monocytes.
Rattan, Vinod, Yamin Shen, Chand Sultana, Dinesh Kumar, and Vijay K.
Kalra.
Departments of Biochemistry and Molecular Biology, and Medicine,
University of Southern California School of Medicine, Los Angeles, CA
90033
APStracts 4:0086E, 1997.
Erythrocytes from patients with diabetes mellitus exhibit an increased
propensity to adhere to cultured human umbilical vein endothelial
cells (HUVEC) as a result of interaction of advanced glycation end
products (AGEs) with their counter receptors (RAGE), contributing to
the pathogenesis of vascular complications. We determined whether the
interaction of diabetic RBC with HUVEC induced cellular oxidant
stress that would culminate in adherence and diapedesis of monocytes,
these being initiating events in endothelial injury and
atherogenesis. We show that the adherence of diabetic RBC (2% Hct),
but not normal RBC, to HUVEC results in a 4-fold increase in the
production of lipid peroxides. Furthermore diabetic RBC-induced
oxidant stress causes a six-fold increase in PECAM-1 phosphorylation
and doubles transendothelial migration of monocyte-like HL-60 cells;
both are blocked by antioxidants and protein kinase C inhibitors. Our
results show that the adherence of diabetic RBC to endothelial cells
initiates a cascade of cellular events resulting in protein kinase C
activation, causing PECAM-1 phosphorylation and concomitant
transendothelial migration of monocytes. The increased diapedesis of
monocytes, brought about by the interaction of diabetic RBC, across
vascular endothelium may play an important role in accelerated
atherosclerosis and cardiovascular disease in diabetics.
Received 21 August 1996; accepted in final form 7 April 1997.
APS Manuscript Number E413-6.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 13 May 1997