title: Subcutaneous Angiotensin II Infusion using Osmotic Pumps Induces Aortic Aneurysms in Mice.
abstract: Osmotic pumps continuously deliver compounds at a constant rate into small animals. This article introduces a standard protocol used to induce aortic aneurysms via subcutaneous infusion of angiotensin II (AngII) from implanted osmotic pumps. This protocol includes calculation of AngII amount and dissolution, osmotic pump filling, implantation of osmotic pumps subcutaneously, observation after pump implantation, and harvest of aortas to visualize aortic aneurysms in mice. Subcutaneous infusion of AngII through osmotic pumps following this protocol is a reliable and reproducible technique to induce both abdominal and thoracic aortic aneurysms in mice. Infusion durations range from a few days to several months based on the purpose of the study. AngII 1,000 ng/kg/min is sufficient to provide maximal effects on abdominal aortic aneurysmal formation in male hypercholesterolemic mouse models such as apolipoprotein E deficient or low-density lipoprotein receptor deficient mice. Incidence of abdominal aortic aneurysms induced by AngII infusion via osmotic pumps is 5-10 times lower in female hypercholesterolemic mice and also lower in both genders of normocholesterolemic mice. In contrast, AngII-induced thoracic aortic aneurysms in mice are not hypercholesterolemia or gender-dependent. Importantly, multiple features of this mouse model recapitulate those of human aortic aneurysms.
authors.forename: Hong
authors.initials: H
authors.lastname: Lu
authors.affiliation: Saha Cardiovascular Research Center, University of Kentucky.
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Howatt
authors.affiliation: Saha Cardiovascular Research Center, University of Kentucky.
authors.forename: Anju
authors.initials: A
authors.lastname: Balakrishnan
authors.affiliation: Saha Cardiovascular Research Center, University of Kentucky.
authors.forename: Jessica J
authors.initials: JJ
authors.lastname: Moorleghen
authors.affiliation: Saha Cardiovascular Research Center, University of Kentucky.
authors.forename: Debra L
authors.initials: DL
authors.lastname: Rateri
authors.affiliation: Department of Pharmacology and Nutritional Sciences, University of Kentucky.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Cassis
authors.affiliation: Saha Cardiovascular Research Center, University of Kentucky; adaugh@uky.edu.
authors.forename: Alan
authors.initials: A
authors.lastname: Daugherty
mesh_terms: D000804:Angiotensin II / Q000008:administration & dosage*; D000818:Animals; D017544:Aortic Aneurysm, Abdominal / Q000139:chemically induced* / Q000378:metabolism; D017545:Aortic Aneurysm, Thoracic / Q000139:chemically induced* / Q000378:metabolism; D001057:Apolipoproteins E / Q000172:deficiency; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000139:chemically induced / Q000378:metabolism; D015918:Infusion Pumps, Implantable; D008297:Male; D051379:Mice; D008822:Mice, Transgenic
chemical_list: D001057:Apolipoproteins E; D000804:Angiotensin II