Differential accumulation of Proteoglycans and hyaluronan in culprit lesions - Insights into plaque erosion

Differential accumulation of Proteoglycans and hyaluronan in culprit lesions - Insights into plaque erosion
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DOI:
10.1161/01.atv.0000034021.92658.4c
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发表时间:
2002-10-01
影响因子:
8.7
通讯作者:
Virmani, R
Virmani, R
中科院分区:
医学1区
文献类型:
--
作者:
Kolodgie, FD;Burke, AP;Virmani, R

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细胞外基质分子多能蛋白聚糖、双糖链蛋白聚糖、核心蛋白聚糖和透明质酸在斑块不稳定性中的重要性尚未被认识到。方法和结果:对具有急性血栓和稳定斑块的冠状动脉病变进行检查,以确定罪犯部位特异性蛋白聚糖和透明质酸的积累和分布。还评估了透明质酸、CD 44和平滑肌(SM)细胞成熟标志物的细胞表面受体。蛋白聚糖和透明质酸积累在不同的模式,这取决于斑块类型。稳定病变的纤维帽富含多能蛋白聚糖和双糖蛋白聚糖,核心蛋白聚糖和透明质酸染色明显较少,而天狼星红显示1型胶原大量积聚。相比之下,在斑块/血栓界面的糜烂中发现了透明质酸和多功能蛋白聚糖的强染色,双糖链蛋白聚糖和核心蛋白聚糖的染色较弱;胶原蛋白含量主要为III型。破裂部位的蛋白多糖或透明质酸的免疫反应性很小。CD 44沿着斑块/血栓界面定位于糜烂中,而在破裂和稳定斑块中,其主要局限于炎性细胞。阳性免疫染色未成熟SM细胞(SM肌球蛋白重链SM 1和SMemb)存在于稳定和侵蚀斑块,而SM 2和smoothelin的存在是弱或不存在的。结论特异性的多功能蛋白聚糖,透明质酸,和CD 44的积累斑块侵蚀的网站牵连这些分子的参与与急性冠状动脉血栓形成相关的事件。
Objective-The importance of the extracellular matrix molecules versican, biglycan, decorin, and hyaluronan in plaque instability has not been recognized.Methods and Results-Coronary lesions with acute thrombi and stable plaques were examined for the accumulation and distribution of specific proteoglycans and hyaluronan at culprit sites. The cell surface receptor for hyaluronan, CD44, and smooth muscle (SM) cell maturation markers were also assessed. Proteoglycans and hyaluronan accumulated in distinct patterns depending on plaque type. The fibrous cap of stable lesions was enriched in versican and biglycan, with considerably less staining for decorin and hyaluronan, whereas picrosirius red revealed a heavy accumulation of collagen type 1. In contrast, intense staining for hyaluronan and versican was found in erosions at the plaque/thrombus interface, with weak staining for biglycan and decorin; collagen content was predominantly type III. Rupture sites showed little immunoreactivity for proteoglycans or hyaluronan. CD44 was localized along the plaque/thrombus interface in erosions, whereas in ruptures and stable plaques, it was mostly confined to inflammatory cells. Positive immunostaining for immature SM cells (SM myosin heavy chain SM1 and SMemb) was present in stable and eroded plaques, whereas the presence of SM2 and smoothelin was weak or nonexistent.Conclusions-Specific accumulation of versican, hyaluronan, and CD44 at the sites of plaque erosion implicates an involvement of these molecules in events associated with acute coronary thrombosis.