title: Influence of apolipoprotein E, age and aortic site on calcium phosphate induced abdominal aortic aneurysm in mice.
abstract: OBJECTIVE
  To assess relevant features of abdominal aortic aneurysms (AAA) induced by calcium phosphate within a mouse model. Specifically we investigated: (1) whether apolipoprotein E deficiency and older age promoted AAA formation, and (2) whether the local application of calcium phosphate affected the size of distant aortic segments.
  
  
  METHODS
  AAA was induced by application of calcium phosphate to the infra-renal aortas of 3 and 7 month old male mice. AAA induction was assessed by calculating expansion of the infra-renal aortic diameter over 1-4 weeks. Aortic samples were assessed to quantify calcification, macrophages infiltration, elastic lamellar degradation and apoptosis. Blood pressure was measured by the tail cuff method, and plasma concentrations of total cholesterol, low density lipoprotein and very low density lipoprotein cholesterol, and pro-inflammatory cytokines were measured using commercially available kits. The maximum diameters of the aortic arch, thoracic and supra-renal aorta at sacrifice were measured by morphometry and the mean maximal diameter of these three aortic segments was calculated.
  
  
  RESULTS
  The median expansion of the infra-renal aorta 2 weeks after AAA induction was significantly greater in apolipoprotein E deficient (ApoE(-/-)) mice than in age- and gender-matched wild type controls [275.8% (IQR 193.8%-348.5%) versus 94.7% (IQR 47.8%-163.4%), P = 0.02]. The greater aortic expansion in ApoE(-/-) mice was associated with aortic calcification, macrophage infiltration, elastic lamellar degradation and apoptosis of cells in the media and adventitia. The plasma low density lipoprotein/very low density lipoprotein cholesterol concentrations 2 weeks after AAA induction were positively correlated with the expansion of the infra-renal aorta induced by calcium phosphate. The median expansion of the infra-renal aorta 2 weeks after AAA induction was similar in 3 and 7 month old wild type mice. The local administration of calcium phosphate was associated with an increase in the mean maximal diameter of distant aortic segments, but not associated with changes in the concentrations of pro-inflammatory markers in either the plasma or the spleen.
  
  
  CONCLUSIONS
  This study suggests that apolipoprotein E deficiency, but not age, predisposes to AAA induced within the calcium phosphate model. Increased AAA expansion in ApoE(-/-) mice was associated with calcification, macrophage infiltration, elastic lamellar degradation, and cell apoptosis. Local application of calcium phosphate also promoted dilation of distant aortic segments.
authors.affiliation: The Vascular Biology Unit, Queensland Research Centre for Peripheral Vascular Disease, School of Medicine and Dentistry, James Cook University, Townsville, Queensland 4811, Australia.
authors.forename: Yutang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: The Vascular Biology Unit, Queensland Research Centre for Peripheral Vascular Disease, School of Medicine and Dentistry, James Cook University, Townsville, Queensland 4811, Australia.
authors.forename: Smriti M
authors.initials: SM
authors.lastname: Krishna
authors.affiliation: The Vascular Biology Unit, Queensland Research Centre for Peripheral Vascular Disease, School of Medicine and Dentistry, James Cook University, Townsville, Queensland 4811, Australia.
authors.forename: Joseph
authors.initials: J
authors.lastname: Moxon
authors.affiliation: The Vascular Biology Unit, Queensland Research Centre for Peripheral Vascular Disease, School of Medicine and Dentistry, James Cook University, Townsville, Queensland 4811, Australia.
authors.forename: Tam Nguyen
authors.initials: TN
authors.lastname: Dinh
authors.affiliation: The Vascular Biology Unit, Queensland Research Centre for Peripheral Vascular Disease, School of Medicine and Dentistry, James Cook University, Townsville, Queensland 4811, Australia.
authors.forename: Roby J
authors.initials: RJ
authors.lastname: Jose
authors.affiliation: The Vascular Biology Unit, Queensland Research Centre for Peripheral Vascular Disease, School of Medicine and Dentistry, James Cook University, Townsville, Queensland 4811, Australia.
authors.forename: Hongyou
authors.initials: H
authors.lastname: Yu
authors.affiliation: The Vascular Biology Unit, Queensland Research Centre for Peripheral Vascular Disease, School of Medicine and Dentistry, James Cook University, Townsville, Queensland 4811, Australia. Electronic address: jonathan.golledge@jcu.edu.au.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Golledge
mesh_terms: D000818:Animals; D001011:Aorta / Q000473:pathology*; D017544:Aortic Aneurysm, Abdominal / Q000097:blood* / Q000235:genetics*; D001057:Apolipoproteins E / Q000097:blood / Q000235:genetics*; D017209:Apoptosis; D001794:Blood Pressure; D002130:Calcium Phosphates / Q000737:chemistry*; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D015243:Cholesterol, VLDL / Q000097:blood; D016207:Cytokines / Q000378:metabolism; D007150:Immunohistochemistry; D007249:Inflammation; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
chemical_list: D001057:Apolipoproteins E; D002130:Calcium Phosphates; D008078:Cholesterol, LDL; D015243:Cholesterol, VLDL; D016207:Cytokines; D002784:Cholesterol; C020243:calcium phosphate
keywords: Abdominal aortic aneurysm; Age; Apolipoprotein E; Calcium phosphate; Cholesterol; Mice