Pericoronary Adipose Tissue as Storage and Supply Site for Oxidized Low-Density Lipoprotein in Human Coronary Plaques
March
Pericoronary Adipose Tissue as Storage and Supply Site for Oxidized Low-Density Lipoprotein in Human Coronary Plaques
Yasumi Uchida 0 1
Yasuto Uchida 1
Ei Shimoyama 1
Nobuyuki Hiruta 1 2
Toshihiko Kishimoto 1
Soichiro Watanabe 1
0 Japanese Foundation for Cardiovascular Research, Funabashi, Japan, 2 Department of Cardiology, Tokyo Jikei University School of Medicine, Tokyo, Japan, 3 Department of Cardiology, Tsukuba Memorial Hospital , Tsukuba , Japan , 4 Department of Pathology, Funabashi-Futawa Hospital , Funabashi , Japan
1 Editor: Xianwu Cheng, Nagoya University , JAPAN
2 Department of Pathology, Toho University Sakura Medical Center, Sakura, Japan, 6 Department of Biomolecular Science, Faculty of Science, Toho University , Okubo, Funabashi , Japan , 7 Department of Biomolecular Science, Faculty of Science, Toho University , Okubo, Funabashi , Japan
Data Availability Statement; All relevant data are within the paper
-
OPEN ACCESS
Abbreviations: PCAT, pericoronary adipose tissue;
NC, necrotic core; oxLDL, oxidized low-density
lipoprotein.
Objectives
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.
Methods
autopsy cases.
Results
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
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.
Conclusions
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.
Introduction
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 [
1–3
], 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 also hypochlorous acid (OHCl) which damages
endothelial cells, resulting in vulnerable plaques [
6–10
].
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. 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.
Using immunohistochemical techniques, the present study was performed to examine
whether and how human PCAT stores and supplies oxLDL to the coronary artery.
Methods
1. Angioscopic and Immunohistochemical Studies of Excised Human
Pericoronary Adipose Tissue (PCAT) and Its Adjacent Coronary Artery
(1). Ethical statement. 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 (...truncated)