| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Outline of Final Research Achievements |
We reported that Hic-5 deficiency resulted in the effective suppression of abdominal aortic aneurysms (AAA) in an animal model. However the role of Hic-5 in thoracic aortic aneurysms (TAA) has not yet been explored. The most common familial TAA is Marfan syndrome (MFS). In this study, we used a murine model of MFS (Fbn1C1039G/+) to generate an MFS murine model in combination with genetic Hic-5 deletion. Fbn1C1039G/+/Hic-5-/- mice displayed more severe dilation of TAA compared with Fbn1C1039G/+ mice. The mRNA and protein expression of several mediators of aortic remodeling, including MMP-2, collagen and elastin, was markedly reduced in the aorta and cultured VSMC from Fbn1C1039G/+/Hic-5-/- mice relative to Fbn1C1039G/+ mice.These results suggest that Hic-5 contributes to extracellular matrix (ECM) synthesis and degradation. Aortic aneurysm is the outcome of the unbalance between ECM synthesis and degradation. The TAA formation in MFS could be more susceptible to defect in ECM synthesis.
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