| Project/Area Number |
23592052
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Thoracic surgery
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
KONDO Takashi 東北大学, 加齢医学研究所, 教授 (10195901)
FUKUMOTO Yoshihiro 久留米大学, 医学部, 教授 (70363372)
NODA Masafumi 東北大学, 大学病院, 講師 (70400356)
OKADA Yoshinori 東北大学, 加齢医学研究所, 准教授 (90323104)
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| Project Period (FY) |
2011 – 2013
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 肺高血圧症 / 酸化ストレス / Nrf2 / 遺伝子改変マウス / 低酸素曝露 / 慢性呼吸器疾患 / 低酸素 / 肺高血圧 / 肺血管リモデリング / tenascin-C / 右心室肥大 / CD31陽性 / 活性化剤 |
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| Research Abstract |
Three weeks of hypoxia exacerbated pulmonary hypertension (PH), right ventricular hypertrophy (RVH), and pulmonary vascular remodeling in mice. These pathological changes were associated with aberrant accumulation of a extracellular glycoprotein, Tenascin-C. Both administration of oltipraz, a potent Nrf2 activator, and Keap1 (negative regulator of Nrf2) knockdown significantly attenuated RVH and pulmonary vascular remodeling and concomitantly ameliorated Tenascin-C accumulation in the hypoxic mouse lungs. Expression of the Nrf2-regulated antioxidant enzymes was decreased in a patient with chronic obstructive pulmonary disease associated with PH. The decreased antioxidant enzymes may underlie the pathogenesis of cardiopulmonary changes in the patient with chronic obstructive pulmonary disease and PH. The efficacy of oltipraz highlights a promising therapeutic potency of Nrf2 activators for the prevention of PH in patients with hypoxemic lung disease.
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