ALDOSTERONE MIGHT BE AN INITIATING FACTOR AND INTERVENTION TARGET IN AORTIC ANEURYSM AND AORTIC DISSECTION

Objective: Previously, we demonstrated that aldosterone (ALD) is associated with aortic aneurysm (AA) or aortic dissection (AD). However, the underlying pathological mechanisms for ALD triggering AA or AD remain elusive. Furthermore, whether ALD antagonists are potential targeted drugs remains unclear. Design and method: Nine-month-old male C57BL/6J mice received ALD and salt for 4 weeks for AA/AD modeling. The ALD antagonist treatment group received spironolactone or finerenone by gavage the morning after ALD osmotic minipump implantation. Immunofluorescence and enzyme-linked immunosorbent assay were performed to evaluate ALD function in AA/AD. Results: The ALD-induced AA/AD specimens had significantly upregulated inflammatory markers (ICAM-1, macrophage-derived LGMN) and oxidative stress marker (ROS) levels compared to healthy aortic tissues. Furthermore, the ALD-induced AA/AD model had significantly upregulated extracellular matrix (ECM) marker (MMP-2) levels. The aortas and plasma of ALD-induced AA and AD mice had reduced vascular smooth muscle (VSMC) contractile markers (CNN1 etc). The ALD antagonist reversed this result.μ Conclusions: This study addressed ALD participation in the main and important pathophysiology mechanisms of AA/AD, including inflammation, oxidative stress, VSMC phenotypic transformation, and ECM degradation. ALD might be the initiating factor for AA/AD and a new intervention target.