Associations of ApoAI and ApoB-containing lipoproteins with AngII-induced abdominal aortic aneurysms in mice. Arterioscler Thromb Vasc Biol 2015 Aug;35(8):1826-34
Date
06/06/2015Pubmed ID
26044581Pubmed Central ID
PMC4514578DOI
10.1161/ATVBAHA.115.305482Scopus ID
2-s2.0-84938062520 (requires institutional sign-in at Scopus site) 33 CitationsAbstract
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.
APPROACH AND 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.
Author List
Liu J, Lu H, Howatt DA, Balakrishnan A, Moorleghen JJ, Sorci-Thomas M, Cassis LA, Daugherty AAuthor
Mary Sorci Thomas PhD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Angiotensin IIAnimals
Anticholesteremic Agents
Aorta, Abdominal
Aortic Aneurysm, Abdominal
Apolipoprotein A-I
Apolipoprotein B-100
Apolipoproteins B
Apolipoproteins E
Azetidines
Diet, Western
Disease Models, Animal
Ezetimibe
Female
Hypercholesterolemia
Male
Mice, Inbred C57BL
Mice, Knockout
Receptors, LDL
Sex Factors
