Role of protein kinase D in vasoconstriction

Research Project

Project/Area Number	17K11058
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Anesthesiology
Research Institution	Yokohama City University
Principal Investigator	MIZUNO Yusuke 横浜市立大学, 附属病院, 准教授 (80433192)
Co-Investigator(Kenkyū-buntansha)	古賀資和横浜市立大学, 医学研究科, 客員研究員 (00637233) 渡辺至横浜市立大学, 医学研究科, 客員教授 (20534142) 川上裕理横浜市立大学, 附属市民総合医療センター, 准教授 (90407958)
Project Period (FY)	2017-04-01 – 2022-03-31
Project Status	Completed (Fiscal Year 2021)
Budget Amount *help	¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000) Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000) Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords	血管収縮 / Protein kinase D / MYPT1 / protein kinase D / 血管平滑筋 / actin / 平滑筋 / カルシウム / アクチン / 肺高血圧 / ROCK
Outline of Final Research Achievements	Protein kinase D (PKD) is known to be involved in a variety of cellular processes and physiological functions, including cell motility, myocardial contraction, angiogenesis, and smooth muscle contraction, but the role of PKD in vascular function has been unknown. We investigated the role of PKD in systemic circulation and aortic contraction in rats and the exact role of PKD isoforms in human aortic smooth muscle cells (HASMCs). We found that PKD1 may be involved in contraction of the aorta and systemic circulation, and that regulation of vasomotor activity by PKD1 may be associated with phosphorylation of MYPT1. Elucidation of PKD may lead to novel regulation of circulation dynamics.
Academic Significance and Societal Importance of the Research Achievements	血管の過剰収縮は高血圧等の様々な病態に関わっており、高血圧の罹患率は我が国では６０歳以上では５０％を超えている。高血圧は心筋梗塞、脳梗塞等の様々な病態を引き起こすため、その予防、治療に多大な医療費が投入されている。しかしながら、血管障害発症の機序は未だ十分には解明されていない。PKDによる血管収縮の発症機序の一端を解明することは、新たな循環動態の制御につながる可能性があり、将来的な血管障害に対する予防治療に貢献する可能性がある。