title: Expression of Vasohibin-1 in Human Carotid Atherosclerotic Plaque.
abstract: OBJECTIVE
  In patients with carotid plaque, intraplaque hemorrhage arising from ruptured neovascular vessels within the neointima is an important cause of stroke. The expression of Vasohibin-1 (VASH1), a negative feedback regulator of angiogenesis, occurs in the microvessel endothelial cells of various solid tumors and the arterial wall. However, the roles of VASH1 in the pathogenesis of atherosclerotic diseases remain unclear. The present study aimed to clarify the relevance of the VASH1 expression and plaque instability in human carotid plaques.
  
  
  METHODS
  We used quantitative real-time PCR and immunostaining to examine 12 atheromatous plaque specimens obtained via carotid endarterectomy. The distal areas of specimens lacking macroscopic atherosclerotic lesions served as controls.
  
  
  RESULTS
  Compared with that observed in the controls, the VASH1 gene expression increased significantly in the atheromatous plaque (p=0.018). Moreover, the VASH1 mRNA levels correlated positively with those of VEGFA, CD31 and VCAM1 (r=0.788, p=0.004; r=0.99, p ＜ 0.001; r=0.94, p ＜ 0.001, respectively). Finally, the immunohistochemical analyses revealed the VASH1 expression in the neointimal microvessel endothelial cells of carotid plaque.
  
  
  CONCLUSIONS
  The VASH1 expression levels in atheroma reflect both enhanced neovascularization and the inflammatory burden. Therefore, the VASH1 level may be a novel biomarker for evaluating plaque instability in patients with carotid arteriosclerosis and predicting ischemic stroke.
authors.affiliation: Department of Neurosurgery, Kyoto University Graduate School of Medicine.
authors.forename: Ryu
authors.initials: R
authors.lastname: Fukumitsu
authors.forename: Manabu
authors.initials: M
authors.lastname: Minami
authors.forename: Kazumichi
authors.initials: K
authors.lastname: Yoshida
authors.forename: Manabu
authors.initials: M
authors.lastname: Nagata
authors.forename: Mika
authors.initials: M
authors.lastname: Yasui
authors.forename: Sei
authors.initials: S
authors.lastname: Higuchi
authors.forename: Risako
authors.initials: R
authors.lastname: Fujikawa
authors.forename: Taichi
authors.initials: T
authors.lastname: Ikedo
authors.forename: Sen
authors.initials: S
authors.lastname: Yamagata
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Sato
authors.forename: Hidenori
authors.initials: H
authors.lastname: Arai
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yokode
authors.forename: Susumu
authors.initials: S
authors.lastname: Miyamoto
mesh_terms: D000368:Aged; D001161:Arteriosclerosis / Q000175:diagnosis; D015415:Biomarkers / Q000378:metabolism; D002339:Carotid Arteries / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D018797:Cell Cycle Proteins / Q000378:metabolism*; D016894:Endarterectomy, Carotid; D042783:Endothelial Cells / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D058226:Plaque, Atherosclerotic / Q000378:metabolism* / Q000503:physiopathology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D015995:Prevalence; D012307:Risk Factors; D020521:Stroke / Q000175:diagnosis; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D015415:Biomarkers; D018797:Cell Cycle Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; C493181:VASH1 protein, human; C467484:VEGFA protein, human; D019010:Vascular Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A