Roles of hydrogen peroxide-induced clone 5 in pathogenesis of thoracic aortic aneurysm in marfan syndrom
Project/Area Number |
26860588
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Cardiovascular medicine
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Research Institution | Showa University |
Principal Investigator |
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Project Period (FY) |
2014-04-01 – 2017-03-31
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Project Status |
Completed (Fiscal Year 2016)
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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)
|
Keywords | 大動脈瘤 / マルファン症候群 / Hic-5 |
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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Report
(4 results)
Research Products
(14 results)
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[Journal Article] The pathophysiological role of oxidized cholesterols in epicardial fat accumulation and cardiac dysfunction: a study in swine fed a high caloric diet with an inhibitor of intestinal cholesterol absorption, ezetimibe.2016
Author(s)
Shimabukuro M, Okawa C, Yamada H, Yanagi S, Uematsu E, Sugasawa N, Kurobe H, Hirata Y, Kim-Kaneyama JR, Lei XF, Takao S, Tanaka Y, Fukuda D, Yagi S, Soeki T, Kitagawa T, Masuzaki H, Sato M, Sata M.
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Journal Title
J Nutr Biochem.
Volume: 35
Pages: 66-73
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Calpain-6 confers atherogenicity to macrophages by dysregulating pre-mRNA splicing.2016
Author(s)
Miyazaki T, Tonami K, Hata S, Aiuchi T, Ohnishi K, Lei XF, Kim-Kaneyama JR, Takeya M, Itabe H, Sorimachi H, Kurihara H, Miyazaki A
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Journal Title
J Clin Invest
Volume: 126
Issue: 9
Pages: 3417-3432
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Calpastatin counteracts pathological angiogenesis by inhibiting suppressor of cytokine signaling 3 degradation in vascular endothelial cells.2015
Author(s)
Miyazaki, T., Taketomi, Y., Saito, Y., Hosono, T., Lei, X.F., Kim-Kaneyama, J.R., Arata, S., Takahashi, H., Murakami, M., and Miyazaki, A.
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Journal Title
Circ. Res.
Volume: 116
Issue: 7
Pages: 1170-1181
DOI
Related Report
Peer Reviewed / Open Access
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