Pasterkamp G, Schoneveld A H, Hijnen D J, de Kleijn D P, Teepen H, van der Wal A C, Borst C
Department of Cardiology, Room G02-523, Heart Lung Institute, Utrecht University Hospital, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.
Atherosclerosis. 2000 Jun;150(2):245-53. doi: 10.1016/s0021-9150(99)00371-8.
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.
动脉粥样硬化管腔狭窄取决于斑块大小和几何重塑模式。最近,我们报道了动脉粥样硬化重塑类型与斑块易损性的组织学标志物的存在有关。炎症和基质降解蛋白酶(MMPs)可能在斑块易损性和动脉扩张性重塑中都起作用。本研究的目的是探讨重塑模式与冠状动脉粥样硬化节段中巨噬细胞和MMPs定位之间的关系。从36条动脉粥样硬化冠状动脉中,分别选取血管面积比相邻节段小>10%和大>10%的节段45个和51个。在扩张性重塑节段和狭窄性重塑节段之间,巨噬细胞染色未观察到显著差异。与狭窄性重塑节段相比,在扩张性重塑节段的斑块中观察到更多的MMP-2和MMP-9染色。一般来说,与斑块相比,外膜层的MMP染色不明显。酶谱分析显示,与狭窄性重塑节段相比,扩张性重塑节段中活性MMP-2更多(分别为340±319和199±181(校正计数/mm(2)),P=0.019)。酶谱分析未显示各组中无活性MMP-2或MMP-9的差异。可以推测,斑块内的MMPs不仅在斑块易损性中起因果作用,而且在新生动脉粥样硬化重塑中也起因果作用。