title: Anti-atherosclerotic effects of pravastatin in brachiocephalic artery in comparison with en face aorta and aortic roots in ApoE/LDLR-/-mice.
abstract: BACKGROUND
  Cholesterol-dependent and independent mechanisms were proposed to explain anti-atherosclerotic action of statins in humans. However, their effects in murine models of atherosclerosis have not been consistently demonstrated. Here, we studied the effects of pravastatin on atherosclerosis in ApoE/LDLR-/-mice fed a control and atherogenic diet.
  
  
  METHODS
  ApoE/LDLR-/-mice were fed a control (CHOW) or an atherogenic (Low Carbohydrate High Protein, LCHP) diet. Two doses of pravastatin (40mg/kg and 100mg/kg) were used. The anti-atherosclerotic effects of pravastatin in en face aorta, cross-sections of aortic roots and brachiocephalic artery (BCA) were analysed. The lipid profile was determined. Fourier Transform Infrared Spectroscopy followed by Fuzzy C-Means (FCM) clustering was used for the quantitative assessment of plaque composition.
  
  
  RESULTS
  Treatment with pravastatin (100mg/kg) decreased total and LDL cholesterol only in the LCHP group, but displayed a pronounced anti-atherosclerotic effect in BCA and abdominal aorta. The anti-atherosclerotic effect of pravastatin (100mg/kg) in BCA was associated with significant alterations of the chemical plaque composition, including a fall in cholesterol and cholesterol esters contents independently on total cholesterol and LDL concentration in plasma.
  
  
  CONCLUSIONS
  Pravastatin at high (100mg/kg), but not low dose displayed a pronounced anti-atherosclerotic effect in ApoE/LDLR-/-mice fed a CHOW or LCHP diet that was remarkable in BCA, visible in en face aorta, whereas it was not observed in aortic roots, suggesting that previous inconsistencies might have been due to the various sites of atherosclerotic plaque analysis.
authors.affiliation: Department of Clinical Biochemistry, Jagiellonian University Medical College, Kopernika 15 A, 31-501 Kraków, Poland. Electronic address: rkostogrys@ar.krakow.pl.
authors.forename: Renata B
authors.initials: RB
authors.lastname: Kostogrys
authors.affiliation: Department of Human Nutrition, Faculty of Food Technology, Agricultural University of Kraków, Balicka 122, 30-149 Kraków, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Franczyk-Zarow
authors.affiliation: Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Bobrzynskiego 14, Kraków, Poland.
authors.forename: Marlena
authors.initials: M
authors.lastname: Gasior-Glogowska
authors.affiliation: Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Bobrzynskiego 14, Kraków, Poland.
authors.forename: Edyta
authors.initials: E
authors.lastname: Kus
authors.affiliation: Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Bobrzynskiego 14, Kraków, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Jasztal
authors.affiliation: Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Bobrzynskiego 14, Kraków, Poland.
authors.forename: Tomasz P
authors.initials: TP
authors.lastname: Wrobel
authors.affiliation: Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Bobrzynskiego 14, Kraków, Poland; Faculty of Chemistry, Jagiellonian University, 3 Ingardena Str., 30-060 Kraków, Poland.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Baranska
authors.affiliation: Department of Human Nutrition, Faculty of Food Technology, Agricultural University of Kraków, Balicka 122, 30-149 Kraków, Poland; Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Bobrzynskiego 14, Kraków, Poland.
authors.forename: Izabela
authors.initials: I
authors.lastname: Czyzynska-Cichon
authors.affiliation: Department of Human Nutrition, Faculty of Food Technology, Agricultural University of Kraków, Balicka 122, 30-149 Kraków, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Drahun
authors.affiliation: Department of Human Nutrition, Faculty of Food Technology, Agricultural University of Kraków, Balicka 122, 30-149 Kraków, Poland.
authors.forename: Angelika
authors.initials: A
authors.lastname: Manterys
authors.affiliation: Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Bobrzynskiego 14, Kraków, Poland; Chair of Pharmacology, Jagiellonian University Medical College, Grzegórzecka 16, 31-531 Kraków, Poland.
authors.forename: Stefan
authors.initials: S
authors.lastname: Chlopicki
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency*; D050197:Atherosclerosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016122:Brachiocephalic Trunk / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005260:Female; D051379:Mice; D018345:Mice, Knockout; D017035:Pravastatin / Q000494:pharmacology / Q000627:therapeutic use*; D011973:Receptors, LDL / Q000172:deficiency*; D016896:Treatment Outcome
chemical_list: D000924:Anticholesteremic Agents; D001057:Apolipoproteins E; D011973:Receptors, LDL; D017035:Pravastatin
keywords: ApoE/LDLR(−/−) mice; Atherosclerosis; Pravastatin