Investigation of cardio-pulmonary disorder in the animal model of sleep apnea syndrome
Project/Area Number |
23590843
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Legal medicine
|
Research Institution | The University of Tokyo |
Principal Investigator |
HISASHI Nagai 東京大学, 医学(系)研究科(研究院), 助教 (60600369)
|
Co-Investigator(Kenkyū-buntansha) |
SHIMOSAWA Tatsuo 東京大学, 医学部附属病院, 講師 (90231365)
|
Co-Investigator(Renkei-kenkyūsha) |
YOSHIDA Kenichi 東京大学, 大学院医学系研究科, 教授 (40166947)
|
Project Period (FY) |
2011 – 2013
|
Project Status |
Completed (Fiscal Year 2013)
|
Budget Amount *help |
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2013: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2011: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
|
Keywords | 睡眠時無呼吸症候群 / 間歇的低酸素 / 肺高血圧 / 低酸素性肺血管収縮 / マクロファージ / 心機能障害 / autophagy / hemoxygenase-1 / intermittent hypoxia / autohagy / heart |
Research Abstract |
In sleep apnea syndrome (SAS), intermittent hypoxia (IH) accompanying sympathoadrenal activation induces repeated episodes of hypoxic pulmonary vasoconstriction (HPV) during sleeping periods, which contributes to pulmonary arterial hypertension (PAH). However, the prevalence of PAH is low and severity is mostly mild in SAS patients. The question then arises as to why PAH is not a universal finding in SAS if repeated hypoxia of sufficient duration causes cycling of HPV. In the present study, we revealed that the repeated HPV is a chief cause of the pathogenesis of PAH in IH and that the circulating monocyte-derived pulmonary M1 macrophages prevent PAH progression by attenuating HPV via beta3AR/iNOS signaling. Here, we propose a new concept that the M1 pulmonary macrophage plays a pivotal role in the control of pulmonary vascular tone and preserving homeostasis of the pulmonary circulation.
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Report
(4 results)
Research Products
(6 results)