Abstract 519: Mineralocorticoid Receptor Agonists and Salt Induce Aortic Aneurysms in C57BL/6 Mice
In an independent study in which we used 10-12 month old male C57BL/6 mice to investigate deoxycorticosterone Acetate (DOCA) and salt (1% saline) induced hypertension, we unexpectedly found that a numbers of mice died of aortic aneurysm rupture. Since aortic aneurysm affects 4-8% elderly men and elevated plasma aldosterone (ALDO) concentrations in patients have been linked to a spectrum of cardiovascular diseases, we therefore tested the possibility that activation of the mineralocorticoid receptor (MR) by DOCA and salt may be involved in aortic aneurysm formation. We reported here that that administration of 10-month-old male C57BL/6 mice with DOCA and salt, but neither DOCA nor salt alone, potently induced abdominal aortic aneurysm (AAA, 62%), thoracic aortic aneurysm (TAA, 44%), and aortic rupture (18%). ALDO and salt also induced similar high rates of AAA (58%), TAA (50%), and aortic rupture (42%). Histological and immunohistological examinations of cross-sections of AAA and TAA at the elastin degradation site demonstrated that DOCA and salt or ALDO and salt induced aortic aneurysm resembled human aortic aneurysm with respect to elastin degradation, macrophage infiltration, smooth muscle cell degeneration and apoptosis, and oxidative stress. Moreover, DOCA and salt also induced aortic aneurysm in 10-week-old mice but with lower incidence and less severe than that in 10-month-old mice. Interestingly, aortic aneurysm formation did not correlate with the increase in blood pressure induced by DOCA and salt. Systemic administration of the angiotensin converting enzyme inhibitor, enalapril, or angiotensin type 1 receptor antagonist, losartan, did not affect DOCA and salt-induced aortic aneurysm. In contrast, the MR antagonist spironolactone significantly attenuated DOCA and salt induced aortic aneurysm. In summary, our study describes a novel aortic aneurysm animal model induced by MR agonist and high salt, and reveals a previously unrecognized but potentially significant role of aldosterone in the pathogenesis of aortic aneurysm. These findings imply that MR antagonists may be effective in the treatment of some aortic aneurysms.
- © 2013 by American Heart Association, Inc.