Affiliation:
1. From the Cardiovascular Division (R.T.L., G.C.C.), Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, and the Dana-Farber Cancer Institute (F.B., M.E.H.), Boston, Mass.
Abstract
Abstract
Vascular smooth muscle cells perform the important function of modulation of vascular extracellular matrix. Because integrins mediate many cell-matrix interactions, the role of integrins in reorganization of collagen by cultured human vascular smooth muscle cells was studied. Immunoprecipitation demonstrated that human vascular smooth muscle cells express multiple β
1
integrins. Monoclonal antibody A2-IIE10 (a blocking anti-α
2
antibody) inhibited adhesion of smooth muscle cells to collagen by 31%. The blocking anti-α
1
antibody 1B3.1 inhibited adhesion by 40%, whereas a blocking anti-α
3
antibody had no effect on adhesion. When 1B3.1 and A2-IIE10 were both used, a 79% reduction in adhesion was observed, indicating that active α
1
and α
2
integrins cooperatively mediate adhesion. The blocking anti-β
1
antibody Mab13 abolished smooth muscle cell–mediated gel contraction, and the α
2
-blocking antibody A2-IIE10 had a dose-dependent partial inhibitory effect (37%). In contrast, blocking antibodies to α
1
and α
3
had no effect. When anti-α
1
(1B3.1) and anti-α
2
(A2-IIE10) monoclonal antibodies were combined, no synergistic effect on inhibition of gel contraction was observed. Surprisingly, collagen gel contraction was inhibited by 46% by an anti-β
1
antibody (TS2/16) known for its stimulatory effect on cell adhesion. Thus, whereas α
1
β
1
and α
2
β
1
integrins both participate in adhesion of vascular smooth muscle cells to collagen, only α
2
β
1
integrins mediate collagen reorganization. In addition, collagen reorganization appears to be a dynamic process, adversely affected by excessive adhesion strengthening.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Cardiology and Cardiovascular Medicine,Physiology
Cited by
116 articles.
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