© 1995 American Heart Association, Inc.
Articles |
Integrin-Mediated Collagen Matrix Reorganization by Cultured Human Vascular Smooth Muscle Cells
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.
Correspondence to Richard T. Lee, MD, Brigham and Women's Hospital, 75 Francis St, Boston, MA 02115.
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 ß1 integrins.
Monoclonal antibody A2-IIE10 (a blocking anti-
2
antibody) inhibited adhesion of smooth muscle cells to collagen by
31%. The blocking anti-1 antibody 1B3.1 inhibited
adhesion by 40%, whereas a blocking anti-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
1 and 2 integrins cooperatively mediate
adhesion. The blocking anti-ß1 antibody Mab13 abolished
smooth muscle cell–mediated gel contraction, and the
2-blocking antibody A2-IIE10 had a dose-dependent
partial inhibitory effect (37%). In contrast, blocking antibodies to
1 and 3 had no effect. When
anti-1 (1B3.1) and anti-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-ß1 antibody
(TS2/16) known for its stimulatory effect on cell adhesion. Thus,
whereas 1ß1 and
2ß1 integrins both participate in adhesion
of vascular smooth muscle cells to collagen, only
2ß1 integrins mediate collagen
reorganization. In addition, collagen reorganization appears to be a
dynamic process, adversely affected by excessive adhesion
strengthening.
Key Words: integrins • atherosclerosis • collagen • vascular smooth muscle • adhesion
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