(Circulation. 2000;101:2949.)
© 2000 American Heart Association, Inc.
Basic Science Reports |
Estrogen Attenuates Integrin-ß3–Dependent Adventitial Fibroblast Migration After Inhibition of Osteopontin Production in Vascular Smooth Muscle Cells
From the Departments of Medicine, Vascular Biology and Hypertension Program, and Surgery, Division of Transplantation, University of Alabama at Birmingham, Birmingham.
Correspondence to Guohong Li, MD, PhD, 1024 Zeigler Research Bldg, 703 S 19th St, Birmingham, AL 35294-0007. E-mail ghli{at}uab.edu
Background—Previous in vitro studies have suggested that estrogen attenuates the vascular injury response by modulating vascular smooth muscle cell (VSMC) expression of soluble factor(s) directing migration of adventitial fibroblasts. Previous in vivo studies have established a role for osteopontin (OPN) and its integrin receptors after vascular injury. In this study, we examined OPN expression in activated VSMCs, its modulation by estrogen, and its effects on adventitial fibroblast migration. In addition, the relative functional roles of ß1- and ß3-integrin–matrix interactions were examined.
Methods and Results—Primary cultures of VSMCs and adventitial
fibroblasts were derived from female Sprague-Dawley rats.
Serum-activated VSMCs expressed high levels of OPN mRNA and
secreted protein that was effectively inhibited by estrogen treatment
(10-7 mol/L). Compared with VSMCs, fibroblasts expressed
similar levels of integrins 
and ß1 and higher
levels of integrin-ß3. Exogenous OPN (5.0 to 40 µg/mL)
directed fibroblast migration in a dose-dependent fashion.
Anti–ß3-integrin antibody (F11) pretreatment markedly
inhibited adventitial fibroblast migration directed by exogenous OPN or
VSMC-conditioned medium in a dose-dependent manner. In contrast,
anti–ß1-integrin antibody (Ha2/5) did not affect
fibroblast migration. Similarly, pretreatment with either linear or
cyclic RGD peptides (10 to 1000 µmol/L) inhibited fibroblast
migration directed by OPN or VSMC-conditioned medium in a
dose-dependent manner.
Conclusions—These observations suggest that estrogen indirectly attenuates integrin-ß3–dependent adventitial fibroblast migration after inhibition of OPN expression in VSMCs.
Key Words: hormones • osteopontin • cells • muscle, smooth • integrins • vasculature
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