Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:54-60
Published online before print October 9, 2003, doi: 10.1161/01.ATV.0000100402.69997.C3
Published online before print October 9, 2003, doi: 10.1161/01.ATV.0000100402.69997.C3
© 2004 American Heart Association, Inc.
Vascular Biology |
Matrix Metalloproteinase-2 and -9 Differentially Regulate Smooth Muscle Cell Migration and Cell-Mediated Collagen Organization
From the Wallace Coulter Department of Biomedical Engineering (C.J.), Georgia Institute of Technology and Emory University School of Medicine, and Division of Cardiology (C.J., Z.S.G.), Emory School of Medicine, Atlanta, Ga.
Correspondence to Zorina S. Galis, PhD, Medicine/Cardiology, 1639 Pierce Dr, WMB 319, Atlanta GA 30322. E-mail zgalis{at}emory.edu
Objectives— Smooth muscle cells (SMCs) produce both matrix metalloproteinase (MMP)-2 and MMP-9, enzymes with similar in vitro matrix degrading abilities. We compared the specific contributions of these enzymes to SMC-matrix interactions in vitro and in vivo.
Methods and Results— Using genetic models of deficiency, we investigated MMP-2 and MMP-9 roles in SMC migration in vivo in the formation of intimal hyperplasia and in vitro. In addition, we investigated potential effects of MMP-2 and MMP-9 genetic deficiency on compaction and assembly of collagen by SMCs.
Conclusions— MMP-2 and MMP-9 genetic deficiency decreased by 81% and 65%, respectively (P<0.01), SMC invasion in vitro and decreased formation of intimal hyperplasia in vivo (P<0.01). However, we found that MMP-9, but not MMP-2, was necessary for organization of collagen by SMCs. Likewise, we found that MMP-9 deficiency resulted in a 50% reduction of SMC attachment to gelatin (P<0.01), indicating that SMCs may use MMP-9 as a bridge between the cell surface and matrix. Furthermore, we found that the hyaluronan receptor, CD44, assists in attachment and utilization of MMP-9 by SMCs. Understanding the specific roles of these MMPs, generally thought to be similar, could improve the design of therapeutic interventions aimed at controlling vascular remodeling.
Key Words: matrix metalloproteinase • smooth muscle cells • vascular remodeling • migration • collagen organization
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