Abstract 64: Serum Amyloid A Augments Angiotensin II-Induced Abdominal Aortic Aneurysm Formation in ApoE-Deficient Mice
Introduction and Objectives: Abdominal aortic aneurysm (AAA), a major cause of death in the aged population, is characterized by vascular inflammation and matrix degradation. Proteolytic enzymes, particularly matrix metalloproteinases (MMP’s), are hypothesized to be active participants in AAA pathogenesis. Serum amyloid A (SAA) is an acute phase reactant that, unlike C-reactive protein (CRP), correlates in humans with aortic dimensions before aneurysm formation. SAA induces MMP expression in cultured cells. In this study we determined whether SAA deficiency in mice altered AAA formation in the well-established angiotensin II (Ang II) infusion model.
Methods and Results: We confirmed that SAA induced MMP-9 and MMP-13 mRNA abundance in J774 macrophage-like cells. Furthermore, we determined for the first time that SAA enhanced MMP-2 activity in cultured mouse abdominal aorta explants. Plasma SAA increased ∼400-fold in apoE-/- mice 24 hours after i.p. Ang II injection (100μg/kg) and ∼12-fold after 28-day Ang II infusion (1000ng/kg/hour). SAA was detected by immunostaining in human AAA tissues and in AAAs of AngII-infused apoE-/- mice. Based on in vivo ultrasound and ex vivo morphological analyses, apoE-/- mice with targeted deletion of SAA (SAAKO; n = 20) exhibited significantly reduced AAA 28 days after Ang II infusion compared to apoE-/- mice that were wild type for SAA (SAAWT; n = 20), despite a modest, but significant increase in the hypertensive response to Ang II. Although the incidence of aortic rupture in SAAKO mice (15%) and SAAWT mice (20%) were similar, the majority of ruptures (75%) in SAAWT mice occurred in the abdominal region, whereas all of the ruptures in the SAAKO mice occurred in the thoracic region. Atherosclerotic lesion area on the luminal surface of the aortic arch was similar in SAAKO and SAAWT mice after Ang II infusion.
Conclusion: Our finding that SAA plays a role in experimental AAA may be pertinent to human studies correlating indexed aortic diameter with plasma SAA concentrations.
- © 2012 by American Heart Association, Inc.