The Role of ATP-Binding Cassette Transporter ABCG2 in thePathophysiology of Cardiovascular Diseases
| Project/Area Number |
23790836
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Project Period (FY) |
2011 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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| Keywords | 心血管病 / 酸化ストレス / 血管新生 / 炎症 / 膜輸送蛋白 / 心肥大 / 血管内皮細胞 / グルタチオン / 動脈硬化 / 分子心臓病態学 |
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| Research Abstract |
To clarify the role of ABCG2 in pressure overload-induced cardiac hypertrophy, we induced pressure overload in wild-type and ABCG2 knockout (KO) mice with transverse aortic constriction (TAC). We found that cardiac hypertrophy and ventricular remodeling after TAC were exacerbated in KO mice. Besides, ABCG2 deficiency exacerbated oxidative stress in the heart tissue during pressure overload. Treatment with antioxidant ameliorated the phenotype in KO mice after TAC. Analysis on genetic expression pattern revealed that antioxidant system is impaired in KO mice. In vitro experiments demonstrated that ABCG2 regulates transport of glutathione, an important endogenous antioxidant, from microvascular endothelial cells. These results indicate that ABCG2 protects against pressure overload-induced cardiac hypertrophy and heart failure by promoting antioxidant response.Next, we assessed the role of ABCG2 in atherosclerosis by using the ischemic model of lower extremities, the wire injury model and cuff implantation model. Although there was no significant difference in angiogenesis between wild-type and KO mice in the ischemic model of lower extremities, atherosclerosis after wire injury or cuff implantation was suppressed in KO mice compared with wild-type mice. Further analyses are necessary to elucidate the mechanisms involved.In summary, we demonstrated that ABCG2 plays a pivotal role in stress response against pathological stimuli and the pathophysiology of cardiovascular diseases.
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Report
(3 results)
Research Products
(10 results)
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[Journal Article] The ATP-binding cassette transporter ABCG2 protects against pressure overload-induced cardiac hypertrophy and heart failure by promoting angiogenesis and antioxidant response2012
Author(s)
Higashikuni Y, Sainz J, Nakamura K, Takaoka M, Enomoto S, Iwata H, Tanaka K, Sahara M, Hirata Y, Nagai R, Sata M
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Journal Title
Arterioscler Thromb Vasc Biol
Volume: 32
Pages: 654-61
Related Report
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[Journal Article] The ATP-binding cassette transporter ABCG2 protects against pressure overload-induced cardiac hypertrophy and heart failure by promoting angiogenesis and antioxidant response2012
Author(s)
Higashikuni Y, Sainz J, Nakamura K, Takaoka M, Enomoto S, Iwata H, Kimie T, Sahara M, Hirata Y, Nagai R, Sata M
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Journal Title
Arterioscler Thromb Vasc Biol
Volume: 32
Issue: 3
Pages: 654-661
DOI
Related Report
Peer Reviewed
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