Abstract 13583: Iron Restriction Reduces Abdominal Aortic Aneurysm Formation in Angiotensin II-Infused Apolipoprotein E Deficient Mice
Background: Abdominal aortic aneurysm (AAA) is a common degenerative vascular disease. However, the exact cause of AAA is unknown. Iron is an essential element for maintaining physiological function in the body, while excess iron leads to tissue damages causing by inflammation. Although inflammation plays a critical role in the pathophysiology of AAA, it has not been investigated whether iron plays a role in AAA. Here, we investigated iron accumulation in AAA tissue and the effects of dietary iron restriction on AAA formation in a mouse model of AAA.
Methods and Results: Ten-week-old male apolipoprotein-E deficient (ApoE-/-) mice were administered angiotensin II (AngII, 1000ng/kg/min) with osmotic minipumps. AngII-administered mice were randomly divided into 2 groups; fed a normal diet (AngII, n=17) or fed an iron-restricted diet (AngII-IR, n=16) for 4 weeks. Saline-infused ApoE-/- mice given a normal diet were served as controls (Control, n=14). Systolic blood pressure was increased similarly in both AngII and AngII-IR mice compared with Control (Control, AngII, AngII-IR; 101±7, 156±5, 157±1mmHg, respectively). AAA formation and aortic rupture occurred in AngII mice (47, 32%, respectively), while iron restriction reduced AAA formation and aortic rupture (6, 0%, respectively, p<0.05). The aortas of AngII mice displayed inflammation, elastin degradation, and adventitial remodeling, along with increased gene expression of monocyte chemotactic protein-1 and collagen type III. In contrast, AngII-IR mice showed well-defined aortic lumen without the increase of these gene expression. Importantly, aortic iron content was increased in AngII mice compared with Control, whereas it was suppressed in AngII-IR mice. Moreover, berlin blue staining revealed that iron was accumulated in the aneurysmal aortic wall of AngII mice, whereas it was not detected in the aortic wall of Control and AngII-IR mice.
Conclusion: Iron restriction reduces AAA formation independent of blood pressure in AngII-infused ApoE-/- mice. These results indicate that iron may play a role in the pathophysiology of AAA.
- © 2013 by American Heart Association, Inc.