徳島大学 教育・研究者情報データベース(EDB)

1. 今西 正樹([徳島大学.大学院医歯薬学研究部.薬学域.先端薬学教育研究プロジェクト]/[徳島大学.大学院医歯薬学研究部.薬学域.薬科学部門.生命薬学系.医薬品機能生化学])

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2. 冨田 修平

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3. 石澤 啓介([徳島大学.大学院医歯薬学研究部.医学域.医科学部門.内科系.臨床薬理学])

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4. 木平 孝高

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5. (英) Ueno Masaki

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6. 石澤 有紀([徳島大学.大学院医歯薬学研究部.医学域.医科学部門.内科系.臨床薬理学]/->個人[井澤 有紀])

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7. 池田 康将([徳島大学.大学院医歯薬学研究部.医学域.医科学部門.生理系.薬理学]/[徳島大学.医学部.医学科.病態情報医学講座.薬理学分野]/[徳島大学.医学研究科.医学専攻.病態情報医学講座]/[徳島大学.大学院医歯薬学研究部.医学域.医科学部門.生理系.薬理学])

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8. 山野 範子

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9. 土屋 浩一郎([徳島大学.大学院医歯薬学研究部.薬学域.薬科学部門.生命薬学系.医薬品機能生化学]/[徳島大学.医学部.医学科.病態情報医学講座])

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10. 玉置 俊晃

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(英) Smooth muscle cell specific Hif-1 deficiency suppresses angiotensin II-induced vascular remodeling in mice

(英) Vascular remodelling is mediated by vascular smooth muscle cell (VSMC) proliferation and hypertrophy, both processes of which are linked to medial thickening and fibrosis. Here, we show that hypoxia-inducible factor-1α (Hif-1α) expressed in smooth muscle cells (SMCs) is involved in angiotensin II (Ang II)-induced vascular remodelling in an in vivo model. To clarify the role of Hif-1α in vascular remodelling, we created mice lacking the Hif-1α gene in SMCs (SMKO mice). Ang II infusion induced medial thickening and vascular fibrosis, accompanied by Hif-1α up-regulation, in the aortae of control mice, but not in those of SMKO mice. In accordance with those results, our in vitro studies showed that the deletion of SMC-derived Hif-1α suppressed the Ang II-induced hypertrophy of VSMCs, and our in vivo studies showed that the Ang II-induced expression of fibrosis-related genes in aortae was suppressed by SMC-specific Hif-1α deficiency. In addition, the SMC-specific Hif-1α deficiency suppressed Ang II-induced macrophage infiltration and Ang II-induced expression of inflammation-related genes in aortae. The superoxide production observed in the aortae of control mice with Ang II was suppressed in those of SMKO mice with Ang II, and this finding was consistent with the results of little Ang II-induced c-Src phosphorylation in SMKO mouse aortae. Loss- and gain-of-function analysis in in vitro experiments confirmed that VSMC-derived Hif-1α functions as an intrinsic modulator of vascular remodelling-related gene expression. Our results revealed that SMC-derived Hif-1α is a crucial mediator of Ang II-induced vascular remodelling.

1. (英) Angiotensin II
2. (英) Animals
3. (英) Fibrosis
4. (英) Gene Expression Regulation
5. (英) Hemodynamics
6. (英) Hypoxia-Inducible Factor 1, alpha Subunit
7. (英) Mice
8. (英) Muscle, Smooth, Vascular
9. (英) Myocytes, Smooth Muscle
10. リン酸化(phosphorylation)
11. (英) Superoxides
12. (英) Vascular Remodeling

1. (英) Article.PublicationTypeList.PublicationType: JOURNAL ARTICLE

2. (英) KeywordList.Keyword: Angiotensin II

3. (英) KeywordList.Keyword: Hypoxia-inducible factor-1 (HIF-1)

4. (英) KeywordList.Keyword: Vascular remodelling

5. (英) KeywordList.Keyword: Vascular smooth muscle