Abstract
ObjectivesIt 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.MethodsLocalization 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.ResultsOxLDL 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.ConclusionsThe 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.
Highlights
The results suggested that pericoronary adipose tissue (PCAT) is a supply source of oxidized low-density lipoprotein (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 molecular therapies targeting the PCAT before plaque growth could be effective in preventing human coronary atherosclerosis
Because voluminous epicardial adipose tissue is a risk factor for coronary events [11], there is a possibility that the pericoronary adipose tissue (PCAT), which is a part of epicardial adipose tissue adjacent to the coronary artery, acts as a risk factor by supplying oxLDL to the adjacent coronary arterial wall
The PCAT releases a number of cytokines which influence coronary function [12] but it is not known whether or not it stores and releases oxLDL to the adjacent coronary arterial intima which is the site of atherosclerosis
Summary
It is generally believed that low-density lipoprotein (LDL) enters the vascular wall from the lumen and is oxidized (oxLDL), after which it plays a key role in the initiation, progression and destabilization of atherosclerotic plaques [1,2,3], and monocytes migrate into the vascular wall from the lumen, and become macrophages [4, 5], that in turn accumulate oxLDL and become foam cells, while producing collagen-degrading enzymes such as metalloproteases and collagenases which destroy collagen fibers, and hypochlorous acid (OHCl) which damages endothelial cells, resulting in vulnerable plaques [6,7,8,9,10].Till date, it is the sole known process of oxLDL generation in vascular wall and it is not known whether there are other mechanisms for oxLDL deposition in the vacular wall in man.Because voluminous epicardial adipose tissue is a risk factor for coronary events [11], there is a possibility that the pericoronary adipose tissue (PCAT), which is a part of epicardial adipose tissue adjacent to the coronary artery, acts as a risk factor by supplying oxLDL to the adjacent coronary arterial wall. 1. Angioscopic and Immunohistochemical Studies of Excised Human Pericoronary Adipose Tissue (PCAT) and Its Adjacent Coronary Artery (1). This ex vivo study was carried out after approval of the Ethical Committees of the Japan Foundation for Cardiovascular Research, Funabashi-Futawa Hospital and Toho University, and after obtaining written informed consent from the families concerned on the use of excised coronary artery and its surrounding adipose tissue for angioscopic and histological studies to clarify the mechanisms of atherosclerosis
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