title: Combination benefit of amlodipine plus atorvastatin treatment on carotid atherosclerosis in Zucker metabolic rats.
abstract: OBJECTIVE
  Obesity is the major risk factor for metabolic syndrome and atherosclerotic cardiocerebrovascular diseases.
  
  
  METHODS
  We studied effects of amlodipine, atorvastatin, and their combination on carotid arteriosclerotic processes in a metabolic syndrome model of Zucker fatty rats. Zucker fatty rats were treated with vehicle, amlodipine, atorvastatin, or combination amlodipine plus atorvastatin for 28 days.
  
  
  RESULTS
  Compared with the single treatment with amlodipine or atorvastatin, the combination of amlodipine plus atorvastatin treatment prevented arteriosclerotic processes, and induced a strong recovery of Sirtuin1 (Sirt1) expression and a marked reduction in p53, p21, and monocyte chemoattractant protein-1 (MCP-1).
  
  
  CONCLUSIONS
  As Sirt1 is a longevity gene that prevents endothelial atherosclerotic processes, and p53, p21, and MCP-1 play pivotal roles in the initiation and development of atherosclerosis, these data suggest a strong synergistic benefit of combination therapy with amlodipine and atorvastatin for preventing atherosclerotic processes, and potentially reducing the clinical risk of cerebrovascular events in metabolic obesity patients.
authors: Depatment of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.
authors: Hiromi
authors: H
authors: Kawai
authors: Tomoko
authors: T
authors: Kurata
authors: Kentaro
authors: K
authors: Deguchi
authors: Shoko
authors: S
authors: Deguchi
authors: Toru
authors: T
authors: Yamashita
authors: Yasuyuki
authors: Y
authors: Ohta
authors: Yoshio
authors: Y
authors: Omote
authors: Syoichiro
authors: S
authors: Kono
authors: Koji
authors: K
authors: Abe
mesh_terms: D017311:Amlodipine / Q000008:administration & dosage*; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage; D000069059:Atorvastatin; D002340:Carotid Artery Diseases / Q000188:drug therapy* / Q000378:metabolism*; D017536:Carotid Artery, Common / Q000187:drug effects* / Q000378:metabolism; D018932:Chemokine CCL2 / Q000096:biosynthesis; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis; D004359:Drug Therapy, Combination; D042783:Endothelial Cells / Q000378:metabolism; D006538:Heptanoic Acids / Q000008:administration & dosage*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage; D008297:Male; D011758:Pyrroles / Q000008:administration & dosage*; D051381:Rats; D056564:Sirtuin 1 / Q000096:biosynthesis; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
chemical_list: D000959:Antihypertensive Agents; D018932:Chemokine CCL2; D050759:Cyclin-Dependent Kinase Inhibitor p21; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D016159:Tumor Suppressor Protein p53; D017311:Amlodipine; D000069059:Atorvastatin; D056564:Sirtuin 1