Abstract 86: Intercellular Adhesion Molecule 1 Deficiency Attenuated Angiotensin II--Induced Abdominal Aortic Aneurysms in Apolipoprotein E--Deficient Mice
Objective: Chronic infusion of angiotensin II (AngII) augments the development of abdominal aortic aneurysms (AAAs) in hypercholesterolemic mice. Several studies have suggested that intercellular adhesion molecule 1 (ICAM-1) expression increases in association with AAA formation. The aim of the study was to define whether ICAM deficiency influenced AngII-induced AAA formation.
Methods and Results: Apolipoprotein E deficient (apoE -/-) mice were cross-bred with ICAM-1 deficient mice. Male apoE -/- mice fed a normal diet and infused subcutaneously with saline or AngII (1,000 ng/kg/min) via osmotic mini pump for 1 week. AngII infusion increased aortic ICAM-1 protein. Male apoE -/- mice that were either ICAM-1 +/+ or -/- were fed a normal diet and infused subcutaneously with AngII (1,000 ng/kg/min) via osmotic mini pump for 4 weeks. Total ICAM-1 deficiency had no significant effect on body weight, total cholesterol concentrations, or systolic blood pressures prior to and during AngII infusion. AngII induced expansion of ex vivo maximal diameters of abdominal aortas was attenuated significantly in ICAM-1 deficient mice (ICAM-1 +/+, 1.78 ± 0.20 mm; ICAM-1 -/-, 1.07 ± 0.03 mm, P < 0.0001). ICAM-1 deficiency also reduced significantly the incidence of AngII-induced AAAs (ICAM-1 +/+, 76%; ICAM-1 -/-, 13%, P < 0.0001). Furthermore, bone-marrow transplantation was performed to develop chimeric mice that were ICAM-1 +/+ or -/- in donor cells and ICAM-1 +/+ or -/- in recipient cells. ICAM-1 deficiency in either donor or recipient cells had no effect on body weight, total cholesterol concentrations, or systolic blood pressure. Recipient ICAM-1 deficiency significantly attenuated the incidence of AngII-induced AAA formation (ICAM-1 +/+, 67%; ICAM-1 -/-, 19%, P = 0.0008). Furthermore, lack of ICAM-1 reduced AngII-induced aortic MMP-2 activation (P < 0.05).
Conclusion: ICAM-1 deficiency attenuated AngII-induced AAAs in male apoE -/- mice.
Author Disclosures: H.A. Uchida: None. R. Umebayashi: None. Y. Kakio: None. K. Shikata: None. H. Makino: None.
- © 2014 by American Heart Association, Inc.