This Article Abstract Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Li, C. Articles by Strauss, B. H. Search for Related Content PubMed PubMed Citation Articles by Li, C. Articles by Strauss, B. H.

Arterial repair after stenting and the effects of gm6001, a matrix metalloproteinase inhibitor

Chris Li, MD^*, Warren J. Cantor, MD, FACC^*, Nafiseh Nili, PhD^*, Ranga Robinson, PhD^*, Louis Fenkell, BSc^*, Yen L. e Tran, BSc^*, Heather A. Whittingham, MSc^*, Winston Tsui, MD^*, Asim N. Cheema, MD^*, John D. Sparkes, MSc^*, Kenneth Pritzker, MD, Daniel E. Levy, PhD and Bradley H. Strauss, MD, PhD, FACC^*,*

^* Roy and Ann Foss Interventional Cardiology Research Program, Terrence Donnelly Heart Center, St. Michael’s Hospital, Toronto, Canada
Department of Laboratory Medicine, Mount Sinai Hospital, University of Toronto, Toronto, Canada
Glycomed, Incorporated, Alameda, California, USA

View larger version (32K): [in a new window]   Figure 1 Schematic diagram outlining study protocol. BA = balloon angioplasty; MMP = matrix metalloproteinase.

View larger version (20K): [in a new window]   Figure 2 Collagen content in the intima (left) and media/adventitia (right). Stented arteries had significant increases in collagen content in the intima at 1 week and 10 weeks and in the media/adventitia at 10 weeks, compared to balloon angioplasty (BA)-treated arteries. +p = 0.006; *p < 0.002.

View larger version (81K): [in a new window]   Figure 3 Gelatin zymogram in balloon angioplasty (BA)-treated and stent arteries. Conditioned medium from chondrocyte cultures were run as positive controls to show 92 kD and 72 kD gelatinolytic activity, which was confirmed by molecular weight markers (not shown). In both BA-treated and stent arteries, 72 kD and 62 kD gelatinolytic bands are evident, corresponding to the pro- and active forms of matrix metalloproteinase (MMP)-2. In stented (but not BA-treated) arteries, an additional gelatinolytic band at 92 kD is evident, corresponding to MMP-9 activity.

View larger version (23K): [in a new window]   Figure 4 Collagen synthesis in cultured smooth muscle cells showed a dose-related inhibition with GM6001. There is >95% inhibition at 1.0 µM. CPM = counts per minute.

View larger version (82K): [in a new window]   Figure 5 Representative photomicrograph of elastic trichrome-stained cross sections of stented arteries showing increased intimal hyerplasia in a placebo-treated artery (A) compared to a GM6001-treated animal (B). 10x objective. I = intima; L = lumen; S = stent strut.

View larger version (16K): [in a new window]   Figure 6 Intimal cross-sectional area (CSA) (A), lumen CSA (B) and intimal collagen content (C) at 10 weeks in stented arteries after treatment with GM6001 or placebo. The CSAs were determined by histomorphometry. The GM6001-treated animals had significant reductions in both intimal CSA and intimal collagen content as well as an increase in lumen CSA. *p < 0.004; p < 0.0002; p = 0.016 compared to placebo-treated animals.