title: Thin-walled microvessels in human coronary atherosclerotic plaques show incomplete endothelial junctions relevance of compromised structural integrity for intraplaque microvascular leakage.
abstract: OBJECTIVE
  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.
authors.affiliation: Maastricht University Medical Center, Department of Pathology, CARIM, the Netherlands.
authors.forename: Judith C
authors.initials: JC
authors.lastname: Sluimer
authors.forename: Frank D
authors.initials: FD
authors.lastname: Kolodgie
authors.forename: Ann P J J
authors.initials: AP
authors.lastname: Bijnens
authors.forename: Kimberly
authors.initials: K
authors.lastname: Maxfield
authors.forename: Erica
authors.initials: E
authors.lastname: Pacheco
authors.forename: Bob
authors.initials: B
authors.lastname: Kutys
authors.forename: Hans
authors.initials: H
authors.lastname: Duimel
authors.forename: Peter M
authors.initials: PM
authors.lastname: Frederik
authors.forename: Victor W M
authors.initials: VW
authors.lastname: van Hinsbergh
authors.forename: Renu
authors.initials: R
authors.lastname: Virmani
authors.forename: Mat J A P
authors.initials: MJ
authors.lastname: Daemen
mesh_terms: D001344:Autopsy; D002102:Cadaver; D002199:Capillary Permeability; D003324:Coronary Artery Disease / Q000473:pathology*; D003331:Coronary Vessels / Q000473:pathology*; D016757:Death, Sudden, Cardiac / Q000473:pathology; D018450:Disease Progression; D004730:Endothelium, Vascular / Q000503:physiopathology* / Q000648:ultrastructure; D004912:Erythrocytes / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007962:Leukocytes / Q000473:pathology; D008297:Male; D008854:Microscopy, Electron; D055806:Microvessels / Q000648:ultrastructure*; D008875:Middle Aged