title: Cholesterol-lowering independent regression and stabilization of atherosclerotic lesions by pravastatin and by antimonocyte chemoattractant protein-1 therapy in nonhuman primates.
abstract: OBJECTIVE
  Anti-atherosclerotic effects of statins might be mediated partly by pleiotropic cholesterol-lowering independent mechanisms. We used nonhuman primates and examined whether treatment with pravastatin or antimonocyte chemoattractant protein-1 (MCP-1) therapy can induce regression and stabilization of established atherosclerotic lesions through cholesterol-lowering independent mechanisms.
  
  
  RESULTS
  Advanced atherosclerosis was induced in the abdominal aorta and the common iliac artery of cynomolgus monkeys by undergoing balloon injury and giving atherogenic diet for 6 months. At 6 months, the diet was changed to normal chow, and the animals were allocated to 4 treatment groups: control vehicle group and other groups treated with pravastatin (1 or 10 mg/kg) or with mutant MCP-1 gene transfection for additional 6 months. Each compound was treated instead of the atherogenic diet, and cholesterol contents in pravastatin-treated groups were adjusted to equalize plasma cholesterol level among groups. Pravastatin reduced neointimal formation in the aorta, but not in the common iliac artery. Pravastatin reduced intimal macrophage area and other markers of plaque destabilization in the common iliac artery. Equivalent inhibitory effects were observed in animals that received mutant MCP-1 gene transfection. No serious side effects were noted by 2 therapeutic modalities.
  
  
  CONCLUSIONS
  This study demonstrated cholesterol-lowering independent regression and stabilization of established atherosclerotic lesions by pravastatin and by anti-MCP-1 therapy in nonhuman primates. An anti-inflammatory mechanism may be involved in the beneficial effects of pravastatin.
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Shiro
authors.initials: S
authors.lastname: Kitamoto
authors.forename: Kaku
authors.initials: K
authors.lastname: Nakano
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Hirouchi
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Kohjimoto
authors.forename: Shunichi
authors.initials: S
authors.lastname: Kitajima
authors.forename: Makoto
authors.initials: M
authors.lastname: Usui
authors.forename: Shujiro
authors.initials: S
authors.lastname: Inoue
authors.forename: Kensuke
authors.initials: K
authors.lastname: Egashira
mesh_terms: D000804:Angiotensin II / Q000097:blood; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D000924:Anticholesteremic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001012:Aorta, Abdominal / Q000293:injuries / Q000473:pathology; D001018:Aortic Diseases / Q000097:blood / Q000188:drug therapy*; D001161:Arteriosclerosis / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D002404:Catheterization; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D002633:Chemotaxis; D002784:Cholesterol / Q000097:blood; D016207:Cytokines / Q000097:blood; D018076:DNA, Complementary / Q000235:genetics; D004036:Diet, Atherogenic; D004353:Drug Evaluation, Preclinical; D015316:Genetic Therapy; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000097:blood / Q000150:complications / Q000188:drug therapy; D007083:Iliac Artery / Q000293:injuries / Q000473:pathology; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000276:immunology; D007249:Inflammation; D008252:Macaca fascicularis; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D010641:Phenotype; D017035:Pravastatin / Q000494:pharmacology* / Q000627:therapeutic use; D011897:Random Allocation; D012083:Renin / Q000097:blood; D014162:Transfection
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000924:Anticholesteremic Agents; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D016207:Cytokines; D018076:DNA, Complementary; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D000804:Angiotensin II; D002784:Cholesterol; D007703:Peptidyl-Dipeptidase A; D012083:Renin; D017035:Pravastatin