Mechanisms which underlie the immediate inhibitory effects by n-3 polyunsaturated fatty acids of coronary artery contraction

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K11519
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: Toho University
• Principal Investigator: TANAKA Yoshio 東邦大学, 薬学部, 教授 (60188349)
• Co-Investigator(Kenkyū-buntansha): 小原 圭将 東邦大学, 薬学部, 講師 (90637422) ; 吉岡 健人 東邦大学, 薬学部, 講師 (50758232)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: n-3系多価不飽和脂肪酸 / 冠動脈 / DHA / EPA / 冠動脈攣縮 / プロスタノイドTP受容体 / U46619 / PGF2α

Outline of Final Research Achievements

We examined whether docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), which are n-3 polyunsaturated fatty acids, exhibited immediate and selective inhibitory effects against prostanoid TP receptor-mediated coronary artery contractions, and whether these inhibitions involved antagonistic actions at TP receptor (TPR). We found that 1) DHA and EPA selectively and potently inhibited TPR-mediated contractions in porcine coronary arteries, which were anatomically and functionally similar to human coronary arteries; 2) DHA and EPA markedly suppressed the increases in intracellular Ca2+ concentrations induced by TP receptor stimulation in human TPR-expressing cells. Based on these findings, we concluded that these immediate TPR antagonistic actions by DHA and EPA could be reflected in their preventing effects against TPR-associated coronary artery spasms.

Free Research Field

薬理学

Academic Significance and Societal Importance of the Research Achievements

DHAやEPAは青み魚やうなぎに豊富に含有される脂肪酸の一種で、心筋梗塞の予防効果をはじめ循環器系疾患に対する予防効果が数多く報告されている。今回私達はヒトの冠動脈と形態学的・機能的に類似しているブタ冠動脈を用いて研究した結果、DHA・EPAが冠動脈攣縮の原因物質と考えられているトロンボキサンA2（TXA2）による収縮を即時的かつ選択的に強力に抑制することを発見し、その機序にTXA2が結合する受容体の遮断作用が関係することを証明した。これにより、DHA・EPAによる心筋梗塞の予防効果の機序の一端が明らかとなり、これらの脂肪酸の摂取の有効性の科学的根拠を示すことができた。