© 1999 American Heart Association, Inc.
Integrative Physiology |
Estradiol Inhibits Leukocyte Adhesion and Transendothelial Migration in Rabbits In Vivo
Possible Mechanisms for Gender Differences in Atherosclerosis
From the Departments of Obstetrics and Gynecology (L.N., S.P., R.S., G.C.) and Molecular and Medical Pharmacology (R.S., G.C.), UCLA School of Medicine, University of California, Los Angeles, Calif, and Department of Pathobiology and Program in Nutritional Sciences (M.R.), University of Washington, Seattle, Wash.
Correspondence to Gautam Chaudhuri, MD, PhD, Departments of Obstetrics and Gynecology, and Molecular and Medical Pharmacology, UCLA School of Medicine, 10833 LeConte Ave, 27-139 CHS, University of California, Los Angeles, CA 90095-1740. E-mail gchaudhu{at}obgyn.medsch.ucla.edu
Abstract—The mechanism by which estrogens protect against atherosclerosis is not known. We evaluated in vivo whether there is a gender difference in monocyte adhesion and subendothelial migration in hypercholesterolemic rabbits and whether any gender differences observed are due to estradiol. Monocyte adhesion and subendothelial migration were assessed in a blinded fashion by analyzing a standardized segment of aorta using a scanning electron microscope. We also assessed whether estradiol modulates induction of vascular cell adhesion molecule-1 (VCAM-1) protein using Western blot and flow cytometric analyses. We observed that male rabbits develop more monocyte adhesion and subendothelial migration than do female rabbits during hypercholesterolemia. We also observed that oophorectomized rabbits given physiological estradiol supplementation demonstrate fewer adherent and subendothelial monocytes than do oophorectomized rabbits given placebo. VCAM-1 protein expression was increased in aortae obtained from hypercholesterolemic, oophorectomized animals supplemented with placebo, and this increase was attenuated by estradiol. Finally, in cultured rabbit aortic endothelial cells stimulated with lysophosphatidylcholine, we observed an increase in VCAM-1 protein that was inhibited in a concentration-dependent fashion by estradiol. We have demonstrated in vivo that there is a gender difference in monocyte adhesion to endothelial cells and transendothelial migration after hypercholesterolemia and that this gender difference is due in part to estradiol. Our results also suggest that estradiol inhibits monocyte adhesion by inhibiting expression of VCAM-1.
Key Words: estrogen • estradiol • atherosclerosis • vascular cell adhesion molecule-1 • monocyte adhesion
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