Introduction
Abdominal aortic aneurysm (AAA) is a complex vascular disease that causes more than 10,000 deaths each year in the United States. Extensive studies have been performed in search of pharmaceutical treatment but surgical repair still remains the most effective treatment. TGF-β signaling is an important mechanism in the pathogenesis of aneurysms; however, there is debate as to whether its role is protective or destructive. Smad3 is a major intracellular mediator of the canonical pathway of TGF-β signaling.
Hypothesis
We hypothesize that Smad3-mediated TGF-β signal pathway plays important roles in the pathogenesis of AAA.
Methods
To test this hypothesis, we analyze the effects of loss of Smad3 on aneurysm formation in the calcium chloride induced AAA model using Smad3 knockout mice.
Results
Three weeks after calcium chloride treatment, the abdominal aorta displayed increased dilation, forming aneurysms. Histology and immunohistochemistry analyses show increased cell proliferation and enhanced inflammatory cell infiltration in the media and adventitia of the vessel wall. This was accompanied by elastic fibers degradation, increased MMPs expression and reduced expression of smooth muscle markers. Further analysis showed that the expression and nuclear localization of Smad2 and Smad4 was significantly increased.
Conclusions
These results demonstrate that Smad3-mediated TGF-β signaling plays a protective role in the pathogenesis of AAA and Smad2/Smad4 upregulation is not sufficient to compensate for the loss of Smad3 in this experimental model.
1% Calcium Chloride Treatment in Combination with Gamma Irradiation Improves Microbial And Physicochemical Properties of Diced Tomatoes
