title: Elsibucol inhibits atherosclerosis following arterial injury: multifunctional effects on cholesterol levels, oxidative stress and inflammation.
abstract: BACKGROUND
  Elsibucol is a metabolically stable derivative of probucol with antioxidant, anti-inflammatory and antiproliferative properties. Here we investigated the effect of elsibucol on the development of atherosclerosis following arterial injury in hypercholesterolemic rabbits.
  
  
  RESULTS
  New Zealand White rabbits were fed a high cholesterol diet that was supplemented or not with 0.5% elsibucol, 1% elsibucol or 1% probucol. An angioplasty of the iliac artery was performed after 3 weeks of diet. We found that treatment with elsibucol significantly decreases blood total cholesterol, LDLc and triglyceride levels. This is associated with a significant 46% reduction of neointimal hyperplasia following arterial injury. Interestingly, the effect of elsibucol on cholesterol levels and neointimal formation appears to be more pronounced than that of probucol. In vitro, elsibucol reduces vascular smooth muscle cell proliferation without affecting cell viability. In vivo, treatment with elsibucol is associated with a significant reduction of cellular proliferation (PCNA immunostaining), oxidative stress (nitrotyrosine immunostaining), VCAM-1 expression and macrophage infiltration in injured arteries. Despite its potent effect on neointimal hyperplasia, elsibucol does not prevent endothelial healing (Evans blue staining) following arterial injury.
  
  
  CONCLUSIONS
  In hypercholesterolemic animals, elsibucol inhibits atherosclerosis and preserves endothelial healing following arterial injury. The mechanisms involved include lowering of blood cholesterol levels together with a reduction of oxidative stress and inflammation in injured arteries.
authors.affiliation: Cardiovascular Research, Centre de Recherche du CHUM (CRCHUM), Montréal, Québec, Canada.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Dussault
authors.affiliation: Cardiovascular Research, Centre de Recherche du CHUM (CRCHUM), Montréal, Québec, Canada.
authors.forename: Wahiba
authors.initials: W
authors.lastname: Dhahri
authors.affiliation: Cardiovascular Research, Centre de Recherche du CHUM (CRCHUM), Montréal, Québec, Canada.
authors.forename: Michel
authors.initials: M
authors.lastname: Desjarlais
authors.affiliation: Cardiovascular Research, Centre de Recherche du CHUM (CRCHUM), Montréal, Québec, Canada.
authors.forename: Raphael
authors.initials: R
authors.lastname: Mathieu
authors.affiliation: Cardiovascular Research, Centre de Recherche du CHUM (CRCHUM), Montréal, Québec, Canada. Electronic address: alain.rivard@umontreal.ca.
authors.forename: Alain
authors.initials: A
authors.lastname: Rivard
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry; D001158:Arteries / Q000473:pathology*; D050197:Atherosclerosis / Q000188:drug therapy*; D002087:Butyrates / Q000627:therapeutic use*; D002339:Carotid Arteries / Q000473:pathology; D049109:Cell Proliferation; D002470:Cell Survival; D002784:Cholesterol / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood; D004730:Endothelium, Vascular / Q000473:pathology; D006937:Hypercholesterolemia / Q000188:drug therapy; D007083:Iliac Artery / Q000473:pathology; D007150:Immunohistochemistry; D007249:Inflammation / Q000097:blood*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D032389:Myocytes, Smooth Muscle / Q000166:cytology; D058426:Neointima / Q000473:pathology; D018384:Oxidative Stress; D010636:Phenols / Q000627:therapeutic use*; D011817:Rabbits; D014652:Vascular Diseases / Q000188:drug therapy*
chemical_list: D000975:Antioxidants; D002087:Butyrates; D008078:Cholesterol, LDL; D010636:Phenols; C487958:elsibucol; D002784:Cholesterol
keywords: Arterial injury; Atherosclerosis; Hypercholesterolaemia; Oxidative stress; Reendothelialisation