我々は, 細胞・組織個々の脂肪酸組成には異なる意義があり, 骨髄由来細胞の脂肪酸組成がω3脂肪酸の心血管保護効果にとって鍵となることを明らかにした。また, LC-MS/MSを用いたリピドミクス解析により, ω3脂肪酸が豊富な環境においてEPA代謝物18-HEPEが選択的に増えており, この脂肪酸代謝物がin vivoおよびin vitroにおいて抗炎症性, 抗線維化活性を有することを明らかにした。18-HEPEの受容体探索を開始し最適な細胞株および刺激分子を選出しており, 現在も探索を継続している。病的心臓組織のMS-imagingを行い, 条件検討が済み, 脂質(リン脂質, 脂肪酸)の画像評価を行っている。
We revealed that the fatty acid composition in each organ and tissue impacted their functional activities and the enrichment of omega-3 fatty acids in bone marrow-derived cells played a key role in the cardioprotective effects of omega-3 fatty acids under pressure overload. LC-MS/MS-based lipidomic analysis of lipid mediator identified 18-HEPE as a major EPA metabolite released by the cardiac macrophages in omega-3 enriched heart. 18-HEPE, which exhibited anti-fibrotic and anti-inflammatory properties in vitro, prevented the pressure overload-induced cardiac remodeling in vivo. These research findings were published in a scientific journal (Endo J et al. J Exp Med. 211(8), 1673-87, 2014). To identify an 18-HEPE specific receptor, we are now searching the cell lines and the stimulants optimized for the receptor screening. Using MS-imaging technique, we are examining the significance of lipid distribution in the pathological heart tissue.
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