Natural progression of atherosclerosis from pathologic intimal thickening to late fibroatheroma in human coronary arteries: A pathology study.
Natural progression of atherosclerosis from pathologic intimal thickening to late fibroatheroma in human coronary arteries: A pathology study.
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DOI：
10.1016/j.atherosclerosis.2015.05.011
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发表时间：
2015-08
期刊：
影响因子：
5.3
通讯作者：
Virmani R
中科院分区：
文献类型：
--
作者：
Otsuka F;Kramer MC;Woudstra P;Yahagi K;Ladich E;Finn AV;de Winter RJ;Kolodgie FD;Wight TN;Davis HR;Joner M;Virmani R
平滑肌细胞、巨噬细胞的浸润和脂质、蛋白聚糖、胶原基质和钙化的积累在动脉粥样硬化中起核心作用。斑块从病理性内膜增厚（PIT）到晚期纤维粥样硬化病变的早期组织学变化尚未完全表征。从67例猝死患者中收集了151例冠状动脉粥样硬化病变。动脉粥样硬化斑块分为无巨噬细胞浸润的PIT、有巨噬细胞浸润的PIT、早期和晚期纤维粥样硬化。巨噬细胞和蛋白聚糖（versican， decorin和biglycan）的存在通过特异性抗体识别，透明质酸通过亲和组织化学检测。油红- o法检测脂质沉积，von Kossa染色和茜素红染色检测钙化。从PIT到晚期纤维粥样硬化的病变进展与巨噬细胞积聚增加（p<0.001）和巨噬细胞清除凋亡小体（吞噬的凋亡小体占总凋亡小体的比例）减少相关（p<0.001）。PIT脂质池的脂质沉积呈微泡状，而坏死核心的脂质沉积呈球状。总的来说，透明质酸（p<0.001）、多聚糖蛋白（p<0.001）和多糖蛋白（p=0.013）的积累随着PIT向纤维粥样硬化的进展而下降。微钙化最初仅在脂质池内观察到，在核心坏死的病变中，微钙化的存在和大小增加。PIT到纤维粥样硬化病变伴有早期脂质积累，随后巨噬细胞浸润，凋亡小体清除缺陷，脂质池中蛋白聚糖和透明质酸减少，转化为坏死核心。钙化始于PIT，并随着斑块的进展而增加。
Smooth muscle cells, macrophage infiltration and accumulation of lipids, proteoglycans, collagen matrix and calcification play a central role in atherosclerosis. The early histologic changes of plaque progression from pathologic intimal thickenings (PIT) to late fibroatheroma lesions have not been fully characterized. A total of 151 atherosclerotic coronary lesions were collected from 67 sudden death victims. Atherosclerotic plaques were classified as PIT without macrophage infiltration, PIT with macrophages, and early and late fibroatheromas. Presence of macrophages and proteoglycans (versican, decorin and biglycan) were recognized by specific antibodies while hyaluronan was detected by affinity histochemistry. Lipid deposition was identified by oil-red-O, and calcification was assessed following von Kossa and alizarin red staining. Lesion progression from PIT to late fibroatheroma was associated with increase in macrophage accumulation (p<0.001) and decreasing apoptotic body clearance by macrophages (ratio of engulfed-to-total apoptotic bodies) (p<0.001). Lipid deposition in lipid pool of PIT had a microvesicular appearance whereas those in the necrotic core were globular in nature. Overall, the accumulation of hyaluronan (p<0.001), and proteoglycan versican (p<0.001) and biglycan (p=0.013) declined along with lesion progression from PIT to fibroatheromas. Microcalcification was first observed only within areas of lipid pools and its presence and size increased in lesions with necrotic core. PIT to fibroatheroma lesions are accompanied by early lipid accumulation, followed by macrophage infiltration with defective clearance of apoptotic bodies along with decrease in proteoglycan and hyaluronan in lipid pools that convert to necrotic cores. Calcification starts in PIT and increases with plaque progression.