Elucidation of pathophysiology for development of new hypertension gene ATP2B1 and carotid atherosclerosis and development of treatment strategy

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09477
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Yokohama City University
• Principal Investigator: Yatsu Keisuke 横浜市立大学, 医学研究科, 客員研究員 (10457856)
• Co-Investigator(Kenkyū-buntansha): 梅村 敏 横浜市立大学, 医学研究科, 客員教授 (00128589) ; 平和 伸仁 横浜市立大学, 附属市民総合医療センター, 准教授 (20315766) ; 岡 晃 東海大学, 総合医学研究所, 講師 (80384866)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: ATP2B1遺伝子 / 本態性高血圧 / 動脈硬化 / CAVI / ノックアウトマウス / カルシウム動態 / 高血圧合併腎疾患 / SNPs

Outline of Final Research Achievements

We identified, a novel hypertension susceptibility gene, ATP2B1 by genome-wide association analysis. This gene encodes PMCA1, which excretes Ca2+ from cells. We created ATP2B1 vascular smooth muscle specific KO mice and whole body ATP2B1 hetero KO mice. We reported that Ca2+ dynamics and alteration of eNOS activity were involved in the mechanism of blood pressure elevation by ATP2B1 and that it is also involved in bone density and PTH secretion. In addition, it was suggested that ATP2B1 is involved in hypertension related renal disease.
Furthermore, in order to investigate the direct relationship between ATP2B1 and atherosclerosis also in human, we have comprehensively analyzed potent ATP2B1 SNPs in people who measured the new atherosclerosis index CAVI.

Free Research Field

高血圧症

Academic Significance and Societal Importance of the Research Achievements

高血圧症は心血管疾患、脳血管障害の重大なリスクの一つである。本態性高血圧の機序解明、治療戦略開拓のため、ヒトゲノムを網羅的に調べ本態性高血圧候補遺伝子として最も関連がある遺伝子としてATP2B1を同定した。この遺伝子が血圧に関与するメカニズムを解明することで本態性高血圧の新たな治療法開発に繋げることができる。さらに、ヒト個々の遺伝子変異、SNPsに応じたテーラーメイド医療の開発に繋げる事ができる。