Abstract 4958: A Novel Mouse Model of Thoracic Aortic Aneurysm Revealed the Protective Property of TNF-alpha Against the Rupture of Aneurysm
Despite high clinical frequencies, precise mechanism in development of aortic aneurysm and dissection remains largely unknown. We recently developed a novel mouse model of constantly producing thoracic aortic aneurysm. A nylon line (0.486mm in diameter) was inserted since the side-branch of femoral artery until the end reached the mid of thoracic aorta. The line was tied and placed in the artery. In wild-type mice, survival rate at 4 weeks after the procedure was 67% (28/42) and thoracic aorta aneurysm developed in 85% (26/28). Massive thoracic hemorrhage indicating aortic rupture was observed in 74% of dead mice (10/14). Proinflammatory genes such as TNF-alpha, MCP1 and IL6 were highly expressed in the aneurysm. Among them, TNF-alpha was constantly and highly expressed shortly (1 day) after the procedure, whereas peak transcriptional levels of other genes were observed at 2 weeks. As the unique temporal gene-expression pattern was observed, we performed this injury model to TNF-alpha-mutant mice. Surprisingly, Kaplan-Mayer analysis showed that survival rate in TNF-alpha-mutant mice was significantly lower in comparison with wild-type mice. 13 of 16 of mice (81%) died within 7 days and survival rate at 4 weeks was 0% (0/16). Histological analysis showed apparent hypocellularity around the injured aorta in TNF-alpha-mutant mice. These results suggest that TNF-alpha might play the role not only in accelerating vascular remodeling, but also in salvage from the aortic rupture in severe injured aorta by accumulating supporting cells.