title: [Prevention of atherosclerotic plaque development by modulating heme oxygenase-1-endogenous carbon monoxide system in rabbit model].
abstract: OBJECTIVE
  To investigate the effect of heme oxygenase/carbon monoxide (HO-1/CO) system on lipid deposition at aortic intima and the mechanism involved in hyperlipidemic rabbits.
  
  
  METHODS
  Totally 32 rabbits, were divided into four groups. One group as control. Three groups for the following treatments: 1.5% cholesterol ration (Ch group, n = 8); 1.5% cholesterol ration plus HO-1 inducer hemin (Hm group, n = 8); and instead of hemin, the HO-1 inhibitor, zinc protoporphyrin IX (Zn group, n = 8) was given by injection into the abdominal cavity. Experiments were lasted for 12 weeks. Rabbit aortas were then isolated as the samples for histopathologic and ultrastructural examination. The protein expressions of HO-1 and endothelin-1 (ET-1) were investigated by immunohistochemical staining and Western blot analysis.
  
  
  RESULTS
  Comparing with the Ch group, rabbits of the Hm group showed a remarkably less extent of lipid deposition at the aortic intima [(17.9 ± 3.0)% vs (54.0 ± 4.2)%], and rabbits of the Zn group had a marked extent of lesion development [(61.1 ± 3.5)%]. Lipid deposition, endothelial damage and neo-intimal formation were less severe in rabbits of the Hm group than those in the Zn or Ch group, respectively. Comparing with the control group, rabbits of the Ch group showed a significant decrease of aortic NO production and cNOS activity. However, there were an enhancement of CO production and HO-1 activity (P < 0.01). Compared with Ch group, rabbits of the Hm group showed a remarkable elevation of aortic HO activity and CO production, whereas rabbits of the Zn group showed a marked decrease of both parameters. Compared with the Ch group, rabbits of the Hm group demonstrated a marked reduction of aorta ET-1 expression, whereas Zn group had a significantly higher ET-1 expression.
  
  
  CONCLUSIONS
  Modulation of HO-1/CO system may improve vascular endothelial function and inhibit smooth muscle cell proliferation in hypercholesterolemic rabbits, likely through a compensatory mechanism and a reduction of ET-1 expression, eventually leading to an inhibition of atherosclerotic plaque development.
authors.affiliation: Department of Cardiology, Affiliated Hospital, Guiyang Medical College, Guiyang, China. liudanan2000@yahoo.com.cn
authors.forename: Da-nan
authors.initials: DN
authors.lastname: Liu
authors.forename: Zuo-yun
authors.initials: ZY
authors.lastname: He
authors.forename: Li-rong
authors.initials: LR
authors.lastname: Wu
authors.forename: Ying
authors.initials: Y
authors.lastname: Fang
authors.forename: Xing-de
authors.initials: XD
authors.lastname: Liu
authors.forename: Ping
authors.initials: P
authors.lastname: Li
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology*; D002248:Carbon Monoxide / Q000378:metabolism*; D002784:Cholesterol / Q000494:pharmacology; D019332:Endothelin-1 / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006427:Hemin / Q000494:pharmacology; D006949:Hyperlipidemias / Q000378:metabolism / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D058226:Plaque, Atherosclerotic / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D011524:Protoporphyrins / Q000494:pharmacology; D011817:Rabbits; D017539:Tunica Intima / Q000378:metabolism / Q000473:pathology*
chemical_list: D019332:Endothelin-1; D004791:Enzyme Inhibitors; D011524:Protoporphyrins; C017803:zinc protoporphyrin; D009569:Nitric Oxide; D006427:Hemin; D002248:Carbon Monoxide; D002784:Cholesterol; D019001:Nitric Oxide Synthase; D051547:Heme Oxygenase-1