Time-Dependent Pathological Changes in Hypoperfusion-Induced Abdominal Aortic Aneurysm

Abstract

Hypoperfusion due to vasa vasorum stenosis can cause wall hypoxia and abdominal aortic aneurysm (AAA) development. Even though hypoperfusion is an important contributor toward pathological changes in AAA, the correlation between hypoperfusion and AAA is not fully understood. In this study, a time-dependent semi-quantitative pathological analysis of hypoperfusion-induced aortic wall changes was performed to understand the mechanisms underlying the gradual degradation of the aortic wall leading to AAA formation. AAA-related factors evaluated in this study were grouped according to the timing of dynamic change, and five groups were formed as follows: first group: angiotensin II type 1 receptor, endothelin-1 (ET-1), and malondialdehyde (MDA); second group: matrix metalloproteinase (MMP)-2, -9, -12, M1 macrophages (Mac387+ cells), and monocyte chemotactic protein-1; third group: synthetic smooth muscle cells (SMCs); fourth group: neutrophil elastase, contractile SMCs, and angiotensinogen; and the fifth group: M2 macrophages (CD163+ cells). Hypoxia-inducible factor-1α, ET-1, MDA, and MMP-9 were colocalized with alpha-smooth muscle actin cells in 3 h, suggesting that hypoperfusion-induced hypoxia directly affects the activities of contractile SMCs in the initial stage of AAA. Time-dependent pathological analysis clarified the cascade of AAA-related factors. These findings provide clues for understanding complicated multistage pathologies in AAA.