title: Mechanisms of aortic and cardiac dysfunction in uremic mice with aortic calcification.
abstract: BACKGROUND
  Chronic renal failure (CRF) is associated with cardiac dysfunction and increased aortic stiffness. The mechanisms involved are not clearly understood. We examined changes over time in cardiac and aortic function in a murine CRF model.
  
  
  RESULTS
  Eight-week-old mice were randomly assigned to 1 of 4 groups: wild-type non-CRF, wild-type CRF, apolipoprotein E knockout non-CRF, and apolipoprotein E knockout CRF. Echocardiography was performed and blood samples were taken at baseline and after 6 and 10 weeks of CRF. Vascular reactivity and adhesion molecule expression were studied after 6 and 10 weeks of CRF. Left ventricular hypertrophy, altered left ventricular relaxation, and increased aortic stiffness were observed after 6 weeks of CRF and persisted after 10 weeks. The 4 groups of mice did not significantly differ in terms of arterial blood pressure and aortic structure. The degree of vascular calcification and serum total cholesterol concentration were higher in the CRF groups than in the non-CRF groups. These changes, however, could not explain the cardiac and vascular differences seen in the 2 CRF groups. In contrast, alterations in vascular reactivity, the upregulation of adhesion molecule expression, and CRF status were significantly associated with these changes.
  
  
  CONCLUSIONS
  In a mouse model of CRF, left ventricular hypertrophy, cardiac diastolic dysfunction, and increased aortic stiffness were not related to structural changes in the aorta (including aortic calcification) or high serum cholesterol levels. However, cardiac and aortic abnormalities were associated with the extent of subendothelial dysfunction and the severity of CRF.
authors.affiliation: INSERM, Unit ERI-12, and Jules Verne University of Picardie and Amiens University Medical Center, Amiens, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Maizel
authors.forename: Isabelle
authors.initials: I
authors.lastname: Six
authors.forename: Michel
authors.initials: M
authors.lastname: Slama
authors.forename: Christophe
authors.initials: C
authors.lastname: Tribouilloy
authors.forename: Henry
authors.initials: H
authors.lastname: Sevestre
authors.forename: Sabrina
authors.initials: S
authors.lastname: Poirot
authors.forename: Philippe
authors.initials: P
authors.lastname: Giummelly
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Atkinson
authors.forename: Gabriel
authors.initials: G
authors.lastname: Choukroun
authors.forename: Michel
authors.initials: M
authors.lastname: Andrejak
authors.forename: Said
authors.initials: S
authors.lastname: Kamel
authors.forename: Jean Claude
authors.initials: JC
authors.lastname: Mazière
authors.forename: Ziad A
authors.initials: ZA
authors.lastname: Massy
mesh_terms: D000818:Animals; D001011:Aorta; D001018:Aortic Diseases / Q000097:blood / Q000503:physiopathology*; D002114:Calcinosis / Q000097:blood / Q000503:physiopathology*; D009202:Cardiomyopathies / Q000097:blood / Q000503:physiopathology; D002784:Cholesterol / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D017379:Hypertrophy, Left Ventricular / Q000097:blood / Q000503:physiopathology; D066298:In Vitro Techniques; D007676:Kidney Failure, Chronic / Q000097:blood / Q000175:diagnosis / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011897:Random Allocation; D014511:Uremia / Q000097:blood / Q000503:physiopathology*
chemical_list: D002784:Cholesterol