The effects of renin-angiotensin system control by HIF-1alpha in arteriosclerosis formation

2014 Fiscal Year Final Research Report

• Project/Area Number: 25860063
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pharmacology in pharmacy
• Research Institution: The University of Tokushima
• Principal Investigator: ISHIZAWA Keisuke 徳島大学, ヘルスバイオサイエンス研究部, 教授 (60398013)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: 血管リモデリング / 動脈硬化 / 血管平滑筋 / Hypoxia inducible factor / アンジオテンシンII / 酸化ストレス / 血管内皮

Outline of Final Research Achievements

Hypoxia-inducible factor-1α (HIF-1α) is a transcription factor which regulates expression levels of a lot of genes implicated in cell proliferation, differentiation, angiogenesis, and so on. Recently, several reports have shown that angiotensin II (Ang II) and cytokines can also induce HIF-1α without hypoxic condition, and thus some reports have suggested that HIF-1α plays crucial roles in chronic inflammation. We have elucidated that Ang II-induced vascular remodeling is suppressed by smooth muscle cell (SMC)-specific HIF-1α deficiency. In our study, we showed that SMC-derived HIF-1α contributes to Ang II-induced vascular smooth muscle cell migration, proliferation and hypertrophy, and vascular fibrosis. We suggested that Ang II-induced SMC-derived HIF-1α expression also contributes to activation of Ang II-AT1 receptor signaling axis. The feedback regulation by HIF-1α may play key roles in Ang II-AT1-induced vascular remodeling.

Free Research Field

薬理学