| Project/Area Number |
14570547
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | SHINSHU UNIVERSITY SCHOOL OF MEDICINE |
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Principal Investigator |
HANAOKA Masayuki SHINSHU UNIVERSITY SCHOOL OF MEDICINE, ASSISTANT PROFESSOR, 医学部, 講師 (20334899)
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| Co-Investigator(Kenkyū-buntansha) |
FUJIMOTO Keisaku SHINSHU UNIVERSITY SCHOOL OF MEDICINE, ASSOCIATE PROFESSOR, 医学部, 助教授 (70242691)
HONDA Takayuki SHINSHU UNIVERSITY SCHOOL OF MEDICINE, ASSOCIATE PROFESSOR, 医学部, 助教授 (80238815)
KUBO Keishi SHINSHU UNIVERSITY SCHOOL OF MEDICINE, PROFESSOR, 医学部, 教授 (80143965)
KOIZUMI Tomonobu SHINSHU UNIVERSITY SCHOOL OF MEDICINE, ASSISTANT PROFESSOR, 医学部附属病院, 講師 (20273097)
OTA Masao SHINSHU UNIVERSITY SCHOOL OF MEDICINE, ASSISTANT PROFESSOR, 医学部, 講師 (50115333)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2003: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | High-altitude pulmonary edema / Vascular endothelial growth factor / Bronchoalveolar lavage / Genetic polymorphism / Endothelial nitric oxide synthase / Tyrosine hydroxylase / Coagulation factor V / Angiotensin-converting enzyme / 健常登山家 / 気管支肺胞洗浄 / 免疫染色 / アンギオテンシン変換酵素 / 肺高血圧 / 高地順応 |
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| Research Abstract |
1.Vascular endothelial growth factor (VEGF) in patients with high-altitude pulmonary edema (HAPE)
Overexpression. of VEGF in the lung is known to induce an increased pulmonary vascular permeability resulting in pulmonary edema. Furthermore, VEGF has been shown to be markedly up-regulated in the hypoxic condition. To examine the role of VEGF in the pathogenesis of RAPE, we measured the concentrations of VEGF in venous serum and bronchoalveolar lavage fluid (BALF) in patients with HAPE and healthy volunteers. The concentration of VEGF in the BALF of patients was markedly deprived compared with that in controls, indicating the production of VEGF is insulted in the lung of the patients. In addition, the deprived VEGF in the BALF of the patients was improved gradually, following a similar VEGF dynamics in venous serum during the stage of recovery.
2.Case-control association studies about the genetic polymorphisms with high-altitude pulmonary edema susceptible subjects (HAPE-s)
1)Endothelial ni
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tric oxide synthase (eNOS) gene
A defect in nitric oxide (NO) synthesis in the lung is considered to contribute to enhance the hypoxic pulmonary vasoconstriction in HAPE-s. We examined two polymorphisms of the eNOS gene, the Glu298Asp variant and 27-basepair (bp) variable numbers of tandem repeats (VNTR), in HAPE-s and healthy climber controls in a Japanese population. We found significant positive associations of the Glu298Asp variant and 27-bp VNTR polymorphism of the eNOS gene with HAPE-s. Moreover, the carriers who possessed simultaneously both of the two significant alleles only existed in HAPE-s group.
2)Tyrosine hydroxylase (TH) gene
A blunted hypoxic ventilatory response (HVR) was observed in HAPE-s and the TH is a rate-limiting enzyme in the carotid body responding to hypoxia to synthesize dopamine neurotransmitter to heighten ventilation. We examined the phenotype of the blunted HVR of HAPE-s with the (TCAT)_n tetranucleotide microsatellite repeats and the Met81Val variant in the TH gene. No significant association regarding either the (TCAT)_n tetranucleotide repeats or the Met81Va1 variant polymorphism of the TH gene was found between HAPE-s and controls.
3)Angiotensin-converting enzyme (ACE) gene
ACE plays an important role in the pathogenesis of pulmonary hypertension that is suggested to be critical in the development of HAPE. The Insertion/Deletion (I/D) polymorphism in ACE gene (ACE-I/D) was investigated by polymerase chain reaction. There was no significant difference of the distribution of the ACE-I/D polymorphism between the HAPE-s and control groups. However, pulmonary vascular resistance and its index on admission were significantly higher in the HAPE-s with D positivity than in the HAPE-s with I positivity. Less
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