Sugita, S.; Kaida, H.; Hayashi, Y.; Yamawaki-Ogata, A.; Nakamura, S.; Ujihara, Y.; Nakamura, M.; Yokota, H.; Narita, Y.

Aims: To elucidate the relationship between interstitial flow (IF) and structural changes in the aortic media during the development of aortic dissection (AD). Methods: Apolipoprotein E-deficient (ApoE[-/-]) mice infused with angiotensin II (AngII) were used as an AD model, in which AD develops exclusively in the thoracoabdominal aorta but not in the thoracic aorta. To capture characteristics present prior to AD onset, the duration of AngII infusion was shortened to generate Pre-AD group. Normal C57BL/6 mice (Normal group) and ApoE(-/-) mice without AngII infusion (Control group) were also included for comparison. Thoracic and thoracoabdominal aortas were excised from all groups, and IF was measured in vitro in accordance with our previously established methods. Results: IF velocity was generally smaller than 4 m/s across all groups; however, velocities exceeding 4 m/s was observed exclusively in the thoracoabdominal region of the Pre-AD group. Although mean IF velocity did not differ significantly among groups, the standard deviation differed significantly and was the highest in the thoracoabdominal region of the Pre-AD group. In this region, IF velocity tended to increase with more prolonged AngII administration, indicating acceleration of IF prior to AD onset. Three-dimensional internal structural microscopy revealed fragmentation of the elastic lamina (ELs) and a reduction in elastin density only in the thoracoabdominal region of the Pre-AD group. Conclusions: Our findings suggest that increased IF and EL degradation occur in parallel and together contribute to the initiation of AD.