Integrative understanding of the development, evolution, disease and regeneration of the coronary circulatory system based on multicellular interaction

2022 Fiscal Year Final Research Report

• Project/Area Number: 19H01048
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Medium-sized Section 53:Organ-based internal medicine and related fields
• Research Institution: The University of Tokyo
• Principal Investigator: Kurihara Hiroki 東京大学, 大学院医学系研究科(医学部), 教授 (20221947)
• Co-Investigator(Kenkyū-buntansha): 富田 幸子 ヤマザキ動物看護大学, 動物看護学部, 教授 (40231451)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 冠動脈 / 発生 / 再生 / 進化 / 病態

Outline of Final Research Achievements

We have revealed that the coronary artery origin is formed through a multi-cellular interaction involving various cell types, including the secondary heart field-derived endothelial cells and neural crest-derived smooth muscle cells, as well as epicardial cells and macrophages, via signals such as endothelin and Sema3E-PlexinD1, during coronary circulation development. In addition, comparative developmental anatomy of vertebrate coronary arteries suggests that the origin of coronary arteries in mammals may be an evolutionary novelty. Furthermore, experiments using a mouse myocardial infarction model revealed that inactivation of Sema3E-PlexinD1 signaling improved the recovery of cardiac function by increasing reactive lymphangiogenesis, leading to therapeutic strategies that target Sema3E-PlexinD1 signaling in coronary　artery diseases.

Free Research Field

分子細胞生物学

Academic Significance and Societal Importance of the Research Achievements

我が国の心疾患による死亡者数はがんに次いで第二位であり、その３分の１以上は冠動脈疾患である。血行再建術などの最近の進歩にもかかわらず、治療が困難な重症例も多く、冠循環系の再生は将来に亘る大きな課題である。本研究は、冠循環系の発生と進化に関して新しい知見と仮説を提示することで、冠動脈疾患の発症基盤や病態生理を理解する上で従来とは異なる新しい視点をもたらすとともに、新しい治療法創出へ向けて重要な基盤を提供するものである。