Adipocyte in vascular wall can induce the rupture of abdominal aortic aneurysm

Abstract

Abdominal aortic aneurysm (AAA) is a vascular disease involving the gradual dilation of the abdominal aorta. It has been reported that development of AAA is associated with inflammation of the vascular wall; however, the mechanism of AAA rupture is not fully understood. In this study, we investigated the mechanism underlying AAA rupture using a hypoperfusion-induced animal model. We found that the administration of triolein increased the AAA rupture rate in the animal model and that the number of adipocytes was increased in ruptured vascular walls compared to non-ruptured walls. In the ruptured group, macrophage infiltration and the protein levels of matrix metalloproteinases 2 and 9 were increased in the areas around adipocytes, while collagen-positive areas were decreased in the areas with adipocytes compared to those without adipocytes. The administration of fish oil, which suppresses adipocyte hypertrophy, decreased the number and size of adipocytes, as well as decreased the risk of AAA rupture ratio by 0.23 compared to the triolein administered group. In human AAA samples, the amount of triglyceride in the adventitia was correlated with the diameter of the AAA. These results suggest that AAA rupture is related to the abnormal appearance of adipocytes in the vascular wall.

Pathological Analysis of the Ruptured Vascular Wall of Hypoperfusion-induced Abdominal Aortic Aneurysm Animal Model

“…Based on the findings of this study and our previous study 8 , we propose a potential mechanism of AAA rupture Fig. 7 .…”

“…7 . Stenosis of the vasa vasorum occurs in the vascular wall during an AAA and leads to the appearance of adipocytes 7,8 . The existence of adipocytes can weaken the arterial wall because the collagen productive cells and collagen fiber are replaced with adipocytes.…”

“…Although our previous study demonstrated that the rupture of AAA may be associated with the abnormal appearance of adipocytes in the vascular wall, histological analysis of a ruptured area has never been performed 8 . In Fig.…”

“…Using a newly established hypoperfusion-induced animal model, we subsequently demonstrated that hypoperfusion of the vascular wall caused AAA development 7 . Histological analysis of the AAA-ruptured vascular walls in the animal model also demonstrated that the abnormal appearance of adipocytes in the vascular wall is associated with AAA rupture 8 . The abnormal appearance of adipocytes was observed and the number of adipocytes in the vascular wall correlated with AAA diameter in humans 8,9 .…”

“…Adipocytes were identified by morphological characteristics that are indicative of adipocytes. We previously identified these cells as adipocytes due to their expression of PPARγ and positive Oil Red O staining 8 . To determine the pathological significance of the presence of adipocytes around the ruptured area, aortic wall areas were divided into four groups as shown in Fig 2d: non-dilated area neck , designated as region 1; dilated area sac without adipocytes, designated as region 2; sac area with adipocytes away from the tear in the aortic wall, designated as region 3; and sac area with adipocytes along the tear in the aortic wall, designated as region 4 Fig.…”