Migration and growth are attenuated in vascular smooth muscle cells with type VIII collagen-null alleles.
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.


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 microm versus 64.2+/-4.4 microm), 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 microm), 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.
Adiguzel
Eser
E
Department of Laboratory Medicine, University of Toronto, Ontario, Canada.
Hou
Guangpei
G
Mulholland
Diane
D
Hopfer
Ulrike
U
Fukai
Naomi
N
Olsen
Bjorn
B
Bendeck
Michelle
M
D000483:Alleles; D000818:Animals; D001011:Aorta / Q000166:cytology; D002455:Cell Division / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D024102:Collagen Type VIII / Q000235:genetics* / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D018715:Microscopy, Video; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000502:physiology*; D015854:Up-Regulation / Q000502:physiology
C507463:Col8a2 protein, mouse; D024042:Collagen Type I; D024102:Collagen Type VIII; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9