title: Associations of ApoAI and ApoB-containing lipoproteins with AngII-induced abdominal aortic aneurysms in mice.
abstract: OBJECTIVE
  Dyslipidemia is implicated in abdominal aortic aneurysms (AAAs) in humans and angiotensin (Ang) II-infused mice. This study determined effects of major lipoprotein classes on AngII-induced AAAs using multiple mouse strains with dietary and pharmacological manipulations.
  
  
  RESULTS
  Western diet had minor effects on plasma cholesterol concentrations and the low incidence of AngII-induced AAAs in C57BL/6J mice. Low incidence of AAAs in this strain was not attributed to protection from high-density lipoprotein, because apolipoprotein (apo) AI deficiency did not increase AngII-induced AAAs. ApoAI deletion also failed to alter AAA occurrence in hypercholesterolemic mice. Low-density lipoprotein receptor-/- mice fed normal diet had low incidence of AngII-induced AAAs. Western diet feeding of this strain provoked pronounced hypercholesterolemia because of increased apoB-containing lipoproteins with attendant increases of atherosclerosis in both sexes, but AAAs only in male mice. ApoE-deficient mice fed normal diet were modestly hypercholesterolemic, whereas this strain fed Western diet was severely hypercholesterolemic because of increased apoB-containing lipoprotein concentrations. The latter augmented atherosclerosis, but did not change the high incidence of AAAs in this strain. To determine whether reductions in apoB-containing lipoproteins influenced AngII-induced AAAs, ezetimibe was administered at a dose that partially reduced plasma cholesterol concentrations to ApoE-deficient mice fed Western diet. This decreased atherosclerosis, but not AAAs. This ezetimibe dose in ApoE-deficient mice fed normal diet significantly decreased plasma apoB-containing lipoprotein concentrations and reduced AngII-induced AAAs.
  
  
  CONCLUSIONS
  ApoB-containing lipoproteins contribute to augmentation of AngII-induced AAA in male mice. However, unlike atherosclerosis, AAA occurrence was not correlated with increases in plasma apoB-containing lipoprotein concentrations.
authors.affiliation: From the Saha Cardiovascular Research Center (J.L., H.L., D.A.H., A.B., J.J.M., A.D.) and Department of Pharmacology and Nutritional Sciences (J.L., L.A.C., A.D.), University of Kentucky, Lexington; and Department of Medicine, Medical College of Wisconsin, Milwaukee (M.S.-T.).
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: From the Saha Cardiovascular Research Center (J.L., H.L., D.A.H., A.B., J.J.M., A.D.) and Department of Pharmacology and Nutritional Sciences (J.L., L.A.C., A.D.), University of Kentucky, Lexington; and Department of Medicine, Medical College of Wisconsin, Milwaukee (M.S.-T.).
authors.forename: Hong
authors.initials: H
authors.lastname: Lu
authors.affiliation: From the Saha Cardiovascular Research Center (J.L., H.L., D.A.H., A.B., J.J.M., A.D.) and Department of Pharmacology and Nutritional Sciences (J.L., L.A.C., A.D.), University of Kentucky, Lexington; and Department of Medicine, Medical College of Wisconsin, Milwaukee (M.S.-T.).
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Howatt
authors.affiliation: From the Saha Cardiovascular Research Center (J.L., H.L., D.A.H., A.B., J.J.M., A.D.) and Department of Pharmacology and Nutritional Sciences (J.L., L.A.C., A.D.), University of Kentucky, Lexington; and Department of Medicine, Medical College of Wisconsin, Milwaukee (M.S.-T.).
authors.forename: Anju
authors.initials: A
authors.lastname: Balakrishnan
authors.affiliation: From the Saha Cardiovascular Research Center (J.L., H.L., D.A.H., A.B., J.J.M., A.D.) and Department of Pharmacology and Nutritional Sciences (J.L., L.A.C., A.D.), University of Kentucky, Lexington; and Department of Medicine, Medical College of Wisconsin, Milwaukee (M.S.-T.).
authors.forename: Jessica J
authors.initials: JJ
authors.lastname: Moorleghen
authors.affiliation: From the Saha Cardiovascular Research Center (J.L., H.L., D.A.H., A.B., J.J.M., A.D.) and Department of Pharmacology and Nutritional Sciences (J.L., L.A.C., A.D.), University of Kentucky, Lexington; and Department of Medicine, Medical College of Wisconsin, Milwaukee (M.S.-T.).
authors.forename: Mary
authors.initials: M
authors.lastname: Sorci-Thomas
authors.affiliation: From the Saha Cardiovascular Research Center (J.L., H.L., D.A.H., A.B., J.J.M., A.D.) and Department of Pharmacology and Nutritional Sciences (J.L., L.A.C., A.D.), University of Kentucky, Lexington; and Department of Medicine, Medical College of Wisconsin, Milwaukee (M.S.-T.).
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Cassis
authors.affiliation: From the Saha Cardiovascular Research Center (J.L., H.L., D.A.H., A.B., J.J.M., A.D.) and Department of Pharmacology and Nutritional Sciences (J.L., L.A.C., A.D.), University of Kentucky, Lexington; and Department of Medicine, Medical College of Wisconsin, Milwaukee (M.S.-T.). Alan.Daugherty@uky.edu.
authors.forename: Alan
authors.initials: A
authors.lastname: Daugherty
mesh_terms: D000804:Angiotensin II; D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology; D001012:Aorta, Abdominal / Q000378:metabolism* / Q000473:pathology; D017544:Aortic Aneurysm, Abdominal / Q000097:blood / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control; D016632:Apolipoprotein A-I / Q000097:blood* / Q000172:deficiency / Q000235:genetics; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B / Q000097:blood*; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D001384:Azetidines / Q000494:pharmacology; D066273:Diet, Western; D004195:Disease Models, Animal; D000069438:Ezetimibe; D005260:Female; D006937:Hypercholesterolemia / Q000097:blood / Q000150:complications* / Q000188:drug therapy / Q000235:genetics; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics; D012737:Sex Factors
chemical_list: D000924:Anticholesteremic Agents; C415826:Apob protein, mouse; D016632:Apolipoprotein A-I; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B; D001057:Apolipoproteins E; D001384:Azetidines; D011973:Receptors, LDL; D000804:Angiotensin II; D000069438:Ezetimibe
keywords: angiotensins; aortic aneurysm; hypercholesterolemia; lipoproteins; receptors, LDL