creation-rodent-model-abdominal-aortic-aneurysm-blocking-adventitial

Creation of a Rodent Model of Abdominal Aortic Aneurysm by Blocking Adventitial Vasa Vasorum Perfusion

The adventitial vasa vasorum (VV) provides oxygen and nourishment to the aortic wall. Hypoxia in the aortic wall can cause enlarged abdominal aortic ...

Kindai University

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.

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

Abdominal aortic aneurysm (AAA) is a vascular disease that results in the gradual dilation of the abdominal aorta and has a high rupture-related mortality rate. However, the mechanism of AAA rupture remains unknown. In our previous study, we established a novel AAA animal model (hypoperfusion-induced AAA rat model) with spontaneous AAA rupture. Using the hypoperfusion-induced AAA rat model, we demonstrated that the abnormal appearance of adipocytes in the vascular wall is associated with AAA rupture. However, pathological analysis of the rupture area has not been performed because it is particularly difficult to identify the rupture point. In this study, we succeeded in obtaining samples from the rupture point and performed a histological analysis of the ruptured area in the vascular wall in the hypoperfusion-induced AAA rat model. Adipocytes were observed along the AAA-ruptured area of the vascular wall. In the areas around the adipocytes, macrophage infiltration and protein levels of matrix metalloproteinases 2 and 9 were significantly increased and collagen-positive areas were significantly decreased, as compared with areas without adipocytes. The AAA diameter was correlated with the number of adipocytes in the vascular wall of the hypoperfusion-induced AAA rat model. On the other hand, serum triglyceride levels and serum total cholesterol levels were not correlated with the number of adipocytes in the vascular wall. These results suggest that local adipocyte accumulation in the vascular wall, not serum lipids, has an important role in AAA rupture.

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

Abdominal aortic aneurysm (AAA) is a vascular disease involving gradual dilation of the abdominal aorta. Recent studies suggest that nicotine, which is a primary component in cigarette smoke, is closely associated with the development and rupture of an AAA. Nicotine accelerates AAA development through the weakening of the vascular wall by increasing oxidative stress and matrix metalloproteinase (MMP)-2 expression. However, little is known about preventing the AAA induced by nicotine. A non-surgical means of preventing the weakening of the vascular wall before the onset of AAA by functional food factors would be a valuable option over surgery. Fish oil is a functional food that is rich in n-3 polyunsaturated fatty acids that have an anti-inflammatory effect. In this study, we evaluated the effect of dietary fish oil on the weakening of the aortic wall due to nicotine administration in a mouse model. Histological analysis showed that the dietary fish oil suppressed the degradation of elastin fibers in the nicotine-administered mice. Additionally, the dietary fish oil suppressed the protein level of MMP-12, macrophage infiltration, and the oxidative stress in the vascular wall. These results suggest that fish oil could suppress the weakening of the vascular wall by suppressing the elastin fiber degradation caused by nicotine. By suppressing the nicotine induced weakening of the vascular wall, fish oil might help prevent the development of AAA.

Suppressive effects of dietary EPA-rich fish oil on the degradation of elastin fibers in the aortic wall in nicotine-administered mice.

Low levels of serum testosterone are characteristically associated with diabetes, coronary atherosclerosis, obstructive sleep apnea, rheumatoid arthritis, and chronic obstructive pulmonary disease. Testosterone replacement therapy is effective against many of these disorders, indicating the importance of maintaining a healthy testosterone level. In this study, we investigated the effects of fish oil on murine testosterone metabolism and analyzed the dynamics of relevant lipids in testes by matrix-assisted laser desorption ionization mass spectrometry imaging. Testosterone was upregulated in mice that received fish oil. In the testicular interstitium, eicosapentaenoic acid-containing phosphatidylcholine was distributed characteristically. These data suggest that eicosapentaenoic acid is involved in testosterone metabolism.

Effect of dietary fish oil on mouse testosterone level and the distribution of eicosapentaenoic acid-containing phosphatidylcholine in testicular interstitium.

Article	Year
Adipocyte in vascular wall can induce the rupture of abdominal aortic aneurysm. Scientific reports\| PubMed ID: 27499372	2016
Pathological Analysis of the Ruptured Vascular Wall of Hypoperfusion-induced Abdominal Aortic Aneurysm Animal Model. Journal of oleo science\| PubMed ID: 28381776	2017
Suppressive effects of dietary EPA-rich fish oil on the degradation of elastin fibers in the aortic wall in nicotine-administered mice. Food & function\| PubMed ID: 28725903	2017
Effect of dietary fish oil on mouse testosterone level and the distribution of eicosapentaenoic acid-containing phosphatidylcholine in testicular interstitium. Biochemistry and biophysics reports\| PubMed ID: 28955915	2016

Hirona Kugo

Biography

JoVE Journal Publications

Other Publications