Uchida Yasumi, Uchida Yasuto, Shimoyama Ei, Hiruta Nobuyuki, Kishimoto Toshihiko, Watanabe Soichiro
Japanese Foundation for Cardiovascular Research, Funabashi, Japan.
Department of Cardiology, Tokyo Jikei University School of Medicine, Tokyo, Japan.
PLoS One. 2016 Mar 24;11(3):e0150862. doi: 10.1371/journal.pone.0150862. eCollection 2016.
It is generally believed that low-density lipoprotein enters the vascular wall from its lumen and oxidized (oxLDL), after which it plays an important role in atherosclerosis. Because voluminous epicardial adipose tissue is a risk factor for coronary events, there is a possibility that the pericoronary adipose tissue (PCAT), which is a part of epicardial adipose tissue, acts as a risk factor by supplying oxLDL to the coronary arterial wall. The present study was performed whether PCAT stores and supplies oxLDL to the coronary wall.
Localization of oxLDL in PCAT and its relation to plaque morphology were examined by immunohistochemical techniques in 27 epicardial coronary arteries excised from 9 human autopsy cases.
OxLDL deposited in all PCAT of the studied cases. The percent (%) incidence of oxLDL in the intima of 25 normal segment, 19 white plaques, 15 yellow plaques without necrotic core (NC) and 10 yellow plaques with NC, was 32, 84, 93 (p<0.05 vs normal segments and yellow plaques with NC), and 30, respectively. OxLDL deposited either in dotted or diffuse pattern. Double immunohistochemical staining revealed that the dotted oxLDL was that contained in CD68(+)-macrophages. The oxLDL-containing macrophages were observed in the interstitial space but not inside of the vasa vasorum, and they traversed PCAT, adventitia, external and internal elastic laminae, suggesting their migration towards the intima. Diffuse oxLDL deposits were observed in 17 preparations, the majority of which were co-localized with the vasa vasorum in outer or in both inner and outer halves of intima, and rarely in the inner half alone.
The results suggested that PCAT is a supply source of oxLDL to coronary intima and acts as a risk factor for coronary events, that oxLDL increasingly deposits in the intima with plaque growth and decreases after plaque maturation, and therefore molecular therapies targeting the PCAT before plaque growth could be effective in preventing human coronary atherosclerosis.
一般认为低密度脂蛋白从管腔进入血管壁并被氧化(oxLDL),之后它在动脉粥样硬化中起重要作用。由于大量的心外膜脂肪组织是冠状动脉事件的危险因素,作为心外膜脂肪组织一部分的冠状动脉周围脂肪组织(PCAT)有可能通过向冠状动脉壁供应oxLDL而成为危险因素。本研究旨在探讨PCAT是否储存并向冠状动脉壁供应oxLDL。
采用免疫组织化学技术,对从9例人类尸检病例中切除的27条心外膜冠状动脉进行研究,检测oxLDL在PCAT中的定位及其与斑块形态的关系。
在所研究病例的所有PCAT中均发现有oxLDL沉积。oxLDL在25个正常节段、19个白色斑块、15个无坏死核心(NC)的黄色斑块和10个有NC的黄色斑块内膜中的发生率(%)分别为32、84、93(与正常节段和有NC的黄色斑块相比,p<0.05)和30。oxLDL以点状或弥漫性模式沉积。双重免疫组织化学染色显示,点状oxLDL存在于CD68(+)巨噬细胞内。含oxLDL的巨噬细胞见于间质间隙,但不见于血管滋养管内部,它们穿过PCAT、外膜、外弹性膜和内弹性膜,提示其向内膜迁移。在17份标本中观察到弥漫性oxLDL沉积,其中大多数在内膜的外半层或内外半层与血管滋养管共定位,很少仅在内半层出现。
结果提示,PCAT是冠状动脉内膜oxLDL的供应源,是冠状动脉事件的危险因素,oxLDL随斑块生长在内膜中沉积增加,斑块成熟后减少,因此在斑块生长前针对PCAT的分子治疗可能对预防人类冠状动脉粥样硬化有效。