人类冠状动脉粥样硬化斑块中的薄壁微血管显示出不完整的内皮连接，这与斑块内微血管渗漏的结构完整性受损有关。

Thin-walled microvessels in human coronary atherosclerotic plaques show incomplete endothelial junctions relevance of compromised structural integrity for intraplaque microvascular leakage.

作者信息

Sluimer Judith C, Kolodgie Frank D, Bijnens Ann P J J, Maxfield Kimberly, Pacheco Erica, Kutys Bob, Duimel Hans, Frederik Peter M, van Hinsbergh Victor W M, Virmani Renu, Daemen Mat J A P

机构信息

Maastricht University Medical Center, Department of Pathology, CARIM, the Netherlands.

出版信息

J Am Coll Cardiol. 2009 Apr 28;53(17):1517-27. doi: 10.1016/j.jacc.2008.12.056.

DOI:10.1016/j.jacc.2008.12.056

PMID:19389562

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2756458/

Abstract

OBJECTIVES

This study sought to examine the ultrastructure of microvessels in normal and atherosclerotic coronary arteries and its association with plaque phenotype.

BACKGROUND

Microvessels in atherosclerotic plaques are an entry point for inflammatory and red blood cells; yet, there are limited data on the ultrastructural integrity of microvessels in human atherosclerosis.

METHODS

Microvessel density (MVD) and ultrastructural morphology were determined in the adventitia, intima-media border, and atherosclerotic plaque of 28 coronary arteries using immunohistochemistry for endothelial cells (Ulex europeaus, CD31/CD34), basement membrane (laminin, collagen IV), and mural cells (desmin, alpha-smooth muscle [SM] actin, smoothelin, SM1, SM2, SMemb). Ultrastructural characterization of microvessel morphology was performed by electron microscopy.

RESULTS

The MVD was increased in advanced plaques compared with early plaques, which correlated with lesion morphology. Adventitial MVD was higher than intraplaque MVD in normal arteries and early plaques, but adventitial and intraplaque MVD were similar in advanced plaques. Although microvessel basement membranes were intact, the percentage of thin-walled microvessels was similarly low in normal and atherosclerotic adventitia, in the adventitia and the plaque, and in all plaque types. Intraplaque microvascular endothelial cells (ECs) were abnormal, with membrane blebs, intracytoplasmic vacuoles, open EC-EC junctions, and basement membrane detachment. Leukocyte infiltration was frequently observed by electron microscopy, and confirmed by CD45RO and CD68 immunohistochemistry.

CONCLUSIONS

The MVD was associated with coronary plaque progression and morphology. Microvessels were thin-walled in normal and atherosclerotic arteries, and the compromised structural integrity of microvascular endothelium may explain the microvascular leakage responsible for intraplaque hemorrhage in advanced human coronary atherosclerosis.

摘要

目的

本研究旨在检查正常和动脉粥样硬化冠状动脉中微血管的超微结构及其与斑块表型的关系。

背景

动脉粥样硬化斑块中的微血管是炎症细胞和红细胞的进入点；然而，关于人类动脉粥样硬化中微血管超微结构完整性的数据有限。

方法

使用针对内皮细胞（欧洲荆豆凝集素、CD31/CD34）、基底膜（层粘连蛋白、IV型胶原）和平滑肌细胞（结蛋白、α-平滑肌肌动蛋白、平滑肌肌动蛋白、SM1、SM2、SMemb）的免疫组织化学方法，测定28条冠状动脉外膜、内膜-中膜边界和动脉粥样硬化斑块中的微血管密度（MVD）和超微结构形态。通过电子显微镜对微血管形态进行超微结构表征。

结果

与早期斑块相比，晚期斑块中的MVD增加，这与病变形态相关。在正常动脉和早期斑块中，外膜MVD高于斑块内MVD，但在晚期斑块中，外膜和斑块内MVD相似。尽管微血管基底膜完整，但在正常和动脉粥样硬化外膜、外膜和斑块以及所有斑块类型中，薄壁微血管的百分比同样较低。斑块内微血管内皮细胞异常，有膜泡、胞质内空泡、开放的内皮细胞-内皮细胞连接和基底膜脱离。通过电子显微镜经常观察到白细胞浸润，并通过CD45RO和CD68免疫组织化学得到证实。