title: Inhibition of Atherosclerosis Progression, Intimal Hyperplasia, and Oxidative Stress by Simvastatin and Ivabradine May Reduce Thoracic Aorta's Stiffness in Hypercholesterolemic Rabbits.
abstract: This study aims to evaluate atherosclerosis, oxidative stress, and arterial stiffness attenuation by simvastatin and ivabradine in hyperlipidemic rabbits.
  
  
  
  Forty rabbits were randomly divided into 4 groups: atherogenic diet (group C), atherogenic diet plus simvastatin (group S), atherogenic diet plus ivabradine (group I), and atherogenic diet plus simvastatin and ivabradine (group S + I). After 9 weeks, rabbits were euthanized and descending aortas excised for mechanical testing. Atherogenic diet induced the development of significant atherosclerotic lesions in group C animals but in none of groups S, I, and S + I. RAM-11 and HHF-35-positive cells were significantly reduced in groups S, I, and S + I compared with group C (P < .001). A significant neointimal hyperplasia and intima-media ratio reduction was demonstrated in groups S (P = .015 and P < .001), I (P = .021 and P < .001), and S + I (P = .019 and P < .001) compared with group C. Protein nitrotyrosine levels were significantly decreased in group S compared with group C (P = .009), and reactive oxygen species levels were decreased in group I compared with group C (P = .011). Aortic stiffness was significantly reduced in groups S, I, and S + I compared with group C (P = .003, P = .011, and P = .029).
  
  
  
  Simvastatin and ivabradine significantly inhibited intimal hyperplasia and oxidative stress contributing to aortic stiffness reduction in hyperlipidemic rabbits.
authors.affiliation: Department of Cardiology, Patras University Hospital, Rion Patras, Greece iokoniari@yahoo.gr.
authors.forename: Ioanna
authors.initials: I
authors.lastname: Koniari
authors.affiliation: Laboratory of Biomechanics and Biomedical Engineering, Department of Mechanical Engineering & Aeronautics, University of Patras, Rion Patras, Greece.
authors.forename: Dimosthenis
authors.initials: D
authors.lastname: Mavrilas
authors.affiliation: Department of Cardiothoracic Surgery, Ioannina University Hospital, Ioannina, Greece.
authors.forename: Efstratios
authors.initials: E
authors.lastname: Apostolakis
authors.affiliation: Laboratory of Molecular Pharmacology, Department of Pharmacy, University of Patras, Patras, Greece.
authors.forename: Evangelia
authors.initials: E
authors.lastname: Papadimitriou
authors.affiliation: Department of Anatomy, School of Medicine, University of Patras, Rion Patras, Greece.
authors.forename: Helen
authors.initials: H
authors.lastname: Papadaki
authors.affiliation: Experimental & Research Center, ELPEN Pharmaceuticals, Athens, Greece.
authors.forename: Apostolos
authors.initials: A
authors.lastname: Papalois
authors.affiliation: Laboratory of Molecular Pharmacology, Department of Pharmacy, University of Patras, Patras, Greece.
authors.forename: Evangelia
authors.initials: E
authors.lastname: Poimenidi
authors.affiliation: Department of Cardiology, Patras University Hospital, Rion Patras, Greece.
authors.forename: Ioanna
authors.initials: I
authors.lastname: Xanthopoulou
authors.affiliation: Department of Cardiology, Patras University Hospital, Rion Patras, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Hahalis
authors.affiliation: Department of Cardiology, Patras University Hospital, Rion Patras, Greece.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Alexopoulos
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D001018:Aortic Diseases / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D001552:Benzazepines / Q000494:pharmacology*; D004036:Diet, Atherogenic; D004195:Disease Models, Animal; D018450:Disease Progression; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006965:Hyperplasia; D000077550:Ivabradine; D008297:Male; D058426:Neointima; D018384:Oxidative Stress / Q000187:drug effects*; D058226:Plaque, Atherosclerotic; D011817:Rabbits; D019821:Simvastatin / Q000494:pharmacology*; D059289:Vascular Stiffness / Q000187:drug effects*
chemical_list: D000975:Antioxidants; D001552:Benzazepines; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000077550:Ivabradine; D019821:Simvastatin
keywords: arterial stiffness; atherosclerosis; ivabradine; oxidative stress; simvastatin