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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:56.)
© 2006 American Heart Association, Inc.

Vascular Biology

Migration and Growth Are Attenuated in Vascular Smooth Muscle Cells With Type VIII Collagen-Null Alleles

Eser Adiguzel; Guangpei Hou; Diane Mulholland; Ulrike Hopfer; Naomi Fukai; Bjorn Olsen; Michelle Bendeck

From the Departments of Laboratory Medicine and Pathobiology and Medicine (E.A., G.H., D.M., M.B.), University of Toronto, Ontario, Canada; the Department of Medicine (U.H.), University of Hamburg, Germany; and the Department of Oral and Developmental Biology (N.F., B.O.), Harvard Medical School, Boston, Mass.

Correspondence to Michelle Bendeck, Department of Laboratory Medicine and Pathobiology, University of Toronto, 1 King’s College Circle, Room 6217, Toronto, Ontario, Canada M5S 1A8. E-mail michelle.bendeck{at}utoronto.ca

Objective— Type VIII collagen is upregulated after vascular injury and in atherosclerosis. However, the role of type VIII collagen endogenously expressed by smooth muscle cells (SMCs) and in the context of the vascular matrix microenvironment, which is rich in type I collagen, is not known. To address this, we have compared aortic SMCs from wild-type (WT) mice to SMCs from type VIII collagen-deficient (KO) mice when plated on type I collagen.

Methods and Results— Type VIII collagen was upregulated after wounding of WT SMCs. KO SMCs exhibited greater adhesion to type I collagen than WT SMCs (optical density [OD₅₉₅]=0.458±0.044 versus 0.193±0.071). By contrast, the WT SMCs spread more (389±75% versus 108±14% increase in cell area), migrated further (total distance 80.6±6.2 µm versus 64.2±4.4 µm), and exhibited increased [³H]-thymidine uptake (160 000±22 300 versus 63 100±12 100 counts per minute) when compared with KO SMCs. Gelatin zymograms showed that WT SMCs expressed latent matrix metalloproteinase 2, whereas KO SMCs did not. Addition of exogenous type VIII collagen returned levels of KO SMC adhesion (OD₅₉₅=0.316±0.038), migration (79.5±5.8 µm), and latent matrix metalloproteinase 2 expression to levels comparable to WT SMCs.

Conclusions— This study suggests that SMCs can modify the matrix microenvironment by producing type VIII collagen, using it to overlay type I collagen, and generating a substrate favorable for migration.

Type VIII collagen is upregulated after vascular injury and in atherosclerosis. Using smooth muscle cells from wild-type and type VIII collagen knockout mice, we show that cells that are able to produce endogenous type VIII collagen, proliferate, spread, and migrate more when the cells are plated on a type I collagen matrix.

Key Words: atherosclerosis • restenosis • collagen • smooth muscle cell migration • MMP

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