Atherosclerotic arterial remodeling and the localization of macrophages and matrix metalloproteases 1, 2 and 9 in the human coronary artery.
Atherosclerotic luminal narrowing is determined by plaque mass and the mode of geometrical remodeling. Recently, we reported that the type of atherosclerotic remodeling is associated with the presence of histological markers for plaque vulnerability. Inflammation and matrix degrading proteases (MMPs) may play a role in both plaque vulnerability and in expansive arterial remodeling. The aim of the present study was to investigate the association between the remodeling mode and the localization of macrophages and MMPs in coronary atherosclerotic segments. From 36 atherosclerotic coronary arteries, 45 and 51 segments were selected with a vessel area that was >10% smaller and larger compared with the adjacent segments, respectively. No significant difference in staining for macrophages was observed between segments with expansive and constrictive remodeling. More MMP-2 and MMP-9 staining was observed in plaques of expansively remodeled segments compared with constrictively remodeled segments. In general, MMP-staining was less evident in the adventitial layer compared with the plaque. Zymography revealed more active MMP-2 in expansively remodeled segments compared with constrictively remodeled segments (340+/-319 vs. 199+/-181 (adjusted counts/mm(2)), respectively, P=0.019). Zymography did not show differences in inactive MMP-2 or MMP-9 among groups. It might be postulated that MMPs within the plaque play a causal role not only in plaque vulnerability but also in de novo atherosclerotic remodeling.
Pasterkamp
G
G
Department of Cardiology, Room G02-523, Heart Lung Institute, Utrecht University Hospital, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands. g.pasterkamp@hli.azu.nl
Schoneveld
A H
AH
Hijnen
D J
DJ
de Kleijn
D P
DP
Teepen
H
H
van der Wal
A C
AC
Borst
C
C
D000368:Aged; D000911:Antibodies, Monoclonal; D015415:Biomarkers; D002102:Cadaver; D003324:Coronary Artery Disease / Q000201:enzymology* / Q000473:pathology; D003331:Coronary Vessels / Q000201:enzymology* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008264:Macrophages / Q000473:pathology*; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000276:immunology / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000276:immunology / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000276:immunology / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D015415:Biomarkers; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1