title: Hypercholesterolemia induces regression in neointimal thickening due to apoptosis of vascular smooth muscle cells in the hamster endothelial injury model.
abstract: OBJECTIVE
  Hypercholesterolemia is a major risk factor in the development of atherosclerosis. Although matrix metalloproteinase may play a key role in plaque rupture, apoptosis of vascular smooth muscle cells (VSMCs), which is induced by cholesterol and its oxides may also contribute to instability and rupture of plaque. Thus, we investigated the roles of hypercholesterolemia in vascular remodeling following endothelial injury in the hamster femoral artery.
  
  
  METHODS
  The endothelium was injured by photochemical reaction between green light and the photosensitizer dye, Rose Bengal. Photochemical reaction is routinely used in our laboratory to produce endothelial injury without mechanical stretching in experimental animals.
  
  
  RESULTS
  In normocholesterolemic hamsters (NCH), neointimal thickening gradually progressed within a 3-week observation period after endothelial injury. In hypercholesterolemic hamsters (HCH), neointimal thickening gradually progressed until the second week after endothelial injury. In contrast, at the third week neointimal thickening regressed and was thinner than that at the second week. There was no significant difference in in vivo proliferation of VSMCs detected by in vivo BrdU uptake between HCH and NCH. Apoptotic cells in the neointima and the media were observed in HCH from 2 to 4 weeks after endothelial injury, but not in NCH. At 2 weeks after endothelial injury, the numbers of TUNEL-positive VSMCs in HCH were significantly higher than those in NCH (neointima; 1.2 +/- 0.3 vs. 0.3 +/- 0.1%, P<0.05, media; 2.9 +/- 0.6 vs. 0.6 +/- 0.2%, P<0.01). Cholesterol deposit, which is detected by oil red O staining was observed in a neointimal or medial area in HCH, but not in NCH.
  
  
  CONCLUSIONS
  These findings suggest that hypercholesterolemia with endothelial injury may induce VSMC apoptosis, followed by the regression of neointimal thickening, further hypercholesteremia might play a role in inducing plaque rupture through apoptosis of VSMC.
authors.affiliation: Department of Pharmacology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, Japan.
authors.forename: Akihisa
authors.initials: A
authors.lastname: Matsuda
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Kazunao
authors.initials: K
authors.lastname: Kondo
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Ikeda
authors.forename: Kazuo
authors.initials: K
authors.lastname: Umemura
mesh_terms: D000818:Animals; D017209:Apoptosis; D002452:Cell Count; D002455:Cell Division; D006224:Cricetinae; D004730:Endothelium, Vascular / Q000293:injuries* / Q000473:pathology; D005263:Femoral Artery; D006937:Hypercholesterolemia / Q000473:pathology*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008264:Macrophages / Q000473:pathology; D008297:Male; D008647:Mesocricetus; D023421:Models, Animal; D009131:Muscle, Smooth, Vascular / Q000473:pathology*; D013997:Time Factors; D017539:Tunica Intima / Q000473:pathology*