2016 Fiscal Year Final Research Report
Roles of hydrogen peroxide-induced clone 5 in pathogenesis of thoracic aortic aneurysm in marfan syndrom
| Project/Area Number |
26860588
|
|---|
| Research Category |
Grant-in-Aid for Young Scientists (B)
|
| Allocation Type | Multi-year Fund |
|---|
| Research Field |
Cardiovascular medicine
|
|---|
| Research Institution | Showa University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2014-04-01 – 2017-03-31
|
| Keywords | 大動脈瘤 |
|---|
| 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.
|
| Free Research Field |
血管生物学
|
