Role of dipeptidyl peptidase III on cardiac pressure overload

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K16086
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Tokyo University of Science (2022); Shiga University of Medical Science (2021)
• Principal Investigator: KOMENO Masahiro 東京理科大学, 薬学部薬学科, 助教 (40866307)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: ジペプチジルペプチダーゼ / 心臓

Outline of Final Research Achievements

We performed Transverse aortic constriction (TAC) on DPPIII knockout mice (DPPIII KO mice) and wild-type mice to create a mouse model of cardiac pressure overload. The effects of DPPIII on cardiac function and pressure loading were examined. DPPIII KO and wild-type TAC mice were followed for 12 weeks by echocardiography for circulatory dynamics. Ejection fraction and fractional shortening were significantly lower in DPPIII KO mice than in wild-type mice after 6 weeks of TAC. In addition, significant thickening was observed in the left ventricular posterior wall, ventricular septal wall, and left ventricular anterior wall thickness compared to the wild type. In histochemical staining, cardiac fibrosis was assessed by picrosirius red staining. DPPIII KO mice heart showed more pronounced heart fibrosis than wild-type mice one .

Free Research Field

病態生化学

Academic Significance and Societal Importance of the Research Achievements

DPPIII は、ジペプチジルペプチダーゼファミリーに属するペプチダーゼであり、DPPIIIは生体内で様々な細胞の細胞質に発現している。本研究の目的は、主としてDPPIIIノックアウトマウスを用いて、心臓への圧負荷状態における心筋DPPIIIの作用機構を明らかにすることである。本研究で心臓機能低下の主因である心圧負荷状態における心筋細胞でのDPPIII の作用機構を分子レベルで明らかにすることができれば、心不全に対する新規治療戦略開発へのアプローチとなるなどの創造性や波及効果が期待できる。