title: The low-dose atorvastatin and valsartan combination effectively protects the arterial wall from atherogenic diet-induced impairment in the guinea pig.
abstract: New preventive strategies for atherosclerosis are needed. In this study, we tested whether a new therapeutic approach consisting of low-dose treatment with a statin and sartan combination could prevent atherogenic diet-induced impairment of the arterial wall in guinea pigs. Twenty-five Dunkin-Hartley guinea pigs were randomly assigned to five experimental groups: 1) normal diet; 2) atherogenic diet (AD); 3) AD + a low-dose atorvastatin and valsartan combination (5mg/kg/day and 2.4mg/kg/day, respectively); 4) AD + low-dose atorvastatin (5mg/kg/day); 5) AD + low-dose valsartan (2.4mg/kg/day). After 8 weeks of treatment, the animals were killed, blood samples collected and thoracic and abdominal aortas isolated. The atherogenic diet significantly impaired maximal thoracic aorta endothelium-dependent relaxation by 40.1% relative to the normal diet. The low-dose combination, compared to the separate drugs, completely preserved thoracic aorta endothelium-dependent relaxation at the level of the group receiving normal diet. This substantial effect was associated with a significant change in the expression of NOS3 (R=0.93; P=0.0002) and IL1b (R=-0.79; P=0.003) genes. In addition, treatment with the low-dose combination or the separate drugs also prevented atherosclerotic plaque formation. We found that treatment with the low-dose atorvastatin and valsartan combination has the capability to completely protect the arterial wall from atherogenic diet-induced damage in the guinea pig model. Further studies evaluating this new therapeutic approach are desirable.
authors.affiliation: Department of Vascular Diseases, University of Ljubljana Medical Centre, Zaloška cesta 7, SI-1000 Ljubljana, Slovenia. Electronic address: miodrag.janic@kclj.si.
authors.forename: Miodrag
authors.initials: M
authors.lastname: Janić
authors.affiliation: Department of Vascular Diseases, University of Ljubljana Medical Centre, Zaloška cesta 7, SI-1000 Ljubljana, Slovenia; Institute of Pharmacology and Experimental Toxicology, Faculty of Medicine, University of Ljubljana, Korytkova 2, SI-1000 Ljubljana, Slovenia. Electronic address: mojca.lunder@mf.uni-lj.si.
authors.forename: Mojca
authors.initials: M
authors.lastname: Lunder
authors.affiliation: Department of Clinical Biochemistry, Faculty of Pharmacy, University of Ljubljana, Askerčeva cesta 7, SI-1000 Ljubljana, Slovenia. Electronic address: janja.zupan@ffa.uni-lj.si.
authors.forename: Janja
authors.initials: J
authors.lastname: Zupan
authors.affiliation: Department of Clinical Biochemistry, Faculty of Pharmacy, University of Ljubljana, Askerčeva cesta 7, SI-1000 Ljubljana, Slovenia. Electronic address: darko.cerne@ffa.uni-lj.si.
authors.forename: Darko
authors.initials: D
authors.lastname: Černe
authors.affiliation: Department of Clinical Biochemistry, Faculty of Pharmacy, University of Ljubljana, Askerčeva cesta 7, SI-1000 Ljubljana, Slovenia. Electronic address: janja.marc@ffa.uni-lj.si.
authors.forename: Janja
authors.initials: J
authors.lastname: Marc
authors.affiliation: Institute of Pharmacology and Experimental Toxicology, Faculty of Medicine, University of Ljubljana, Korytkova 2, SI-1000 Ljubljana, Slovenia. Electronic address: gorazd.drevensek@mf.uni-lj.si.
authors.forename: Gorazd
authors.initials: G
authors.lastname: Drevenšek
authors.affiliation: Department of Vascular Diseases, University of Ljubljana Medical Centre, Zaloška cesta 7, SI-1000 Ljubljana, Slovenia. Electronic address: miso.sabovic@kclj.si.
authors.forename: Mišo
authors.initials: M
authors.lastname: Šabovič
mesh_terms: D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects* / Q000378:metabolism; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism; D050197:Atherosclerosis / Q000188:drug therapy / Q000378:metabolism; D000069059:Atorvastatin; D004036:Diet, Atherogenic / Q000379:methods; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D006168:Guinea Pigs; D006538:Heptanoic Acids / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D058226:Plaque, Atherosclerotic / Q000188:drug therapy* / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology*; D013777:Tetrazoles / Q000494:pharmacology*; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000068756:Valsartan
chemical_list: D006538:Heptanoic Acids; D053583:Interleukin-1beta; D020011:Protective Agents; D011758:Pyrroles; D013777:Tetrazoles; D000068756:Valsartan; D000069059:Atorvastatin; D052250:Nitric Oxide Synthase Type III; D014633:Valine
keywords: Atherogenic diet; Atherosclerosis; Guinea pig atherosclerosis model; Prevention; Sartan; Statin