Dysfunction of STIM1 and Hypertesnion: evaluation using a novel genome-edited SHRSP
| Project/Area Number |
17K08787
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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 |
Experimental pathology
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| Research Institution | Shimane University |
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Principal Investigator |
Ohara Hiroki 島根大学, 学術研究院医学・看護学系, 助教 (10609225)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 高血圧 / ストレス / 交感神経 / 脳卒中易発症高血圧自然発症ラット / Stim1 / CRISPR/Cas9 / 脳卒中易発症高血圧自然発症ラット(SHRSP) / 脳卒中 / SHRSP / コンジェニック系統 / 疾患モデル動物 |
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| Outline of Final Research Achievements |
Sympathetic hyperactivities have been thought to be a plausible genetic factor responsible for hereditary severe hypertension in stroke-prone spontaneously hypertensive rats (SHRSP). We previously identified stromal interaction molecule 1 (Stim1), in which SHRSP had a nonsense mutation, as a possible candidate gene causally related to exaggerated sympathetic response to stress in SHRSP. In the current study, we created a genome-edited SHRSP which was knocked-in with the wild-type Stim1 by the CRISPR/Cas9 method to investigate whether the functional recovery of STIM1 would mitigate sympatho-excitation to stress in vivo in SHRSP. Unexpectedly, the Stim1 knock-in SHRSP did not show any significant reduction in stress responsiveness (urinary norepinephrine and blood pressure elevation under stress) except for HR under restraint stress condition. In conclusion, the results indicated that Stim1 is not major genetic determinant related to sympathetic hyperresponse to stress in SHRSP.
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| Academic Significance and Societal Importance of the Research Achievements |
現代人は少なからず何らかの環境的・社会的ストレスに晒されており、これにより生じる高血圧病態が脳心血管病の危険因子となることが疫学的に指摘されている。多すぎるほどの物や情報が溢れる現代社会で、ストレスから完全に逃れることは困難であり、ストレス反応をうまく制御することが重要となる。ストレス感受性は個々人で異なり、感受性が高く昇圧が（過剰に）起こりやすい人もいれば、そうでない人もいる。本研究成果は、ヒト本態性高血圧のモデル動物において、ストレス刺激に対する過剰な交感神経反応を引き起こすメカニズムを解明することで、ストレス制御による新たな高血圧治療法とヒト脳心血管病予防法を開発することに貢献する。
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Report
(4 results)
Research Products
(7 results)
