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12-HEPE promotes cardiomyocyte proliferation by activating glycolysis and histone lactylation via Hippo signaling

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机构： [1]Department of Cardiology & Hongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, 1111 Xianxia Road, Shanghai, 200336, China.

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关键词： Cardiomyocyte proliferation Glycolysis 12-HEPE

摘要：

The regenerative capacity of the adult mammalian heart is limited, while neonatal hearts exhibit regenerative potential during the first postnatal week, driven by cardiomyocyte (CM) proliferation. This capacity declines with metabolic shifts, but the role of metabolites in CM proliferation remains unclear. Using LC-MS/MS, we identified lower levels of 12-HEPE, an omega-3 fatty acid metabolite, in postnatal day 7 (P7) and compared to postnatal day 1 (P1) mouse hearts. Supplementation of 12-HEPE has a positive effect on CM proliferation both in vivo and in vitro. Mechanistically, 12-HEPE activates the Hippo pathway to enhance CM glycolysis, thereby promoting CM proliferation. Moreover, 12-HEPE regulates the cell cycle by modulating H3K18la lactylation. These results suggest 12-HEPE as a key pro-proliferative metabolite and a potential therapeutic target for heart regeneration.Copyright © 2025 Elsevier B.V. All rights reserved.

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出版当年[2025]版：

大类 | 3 区医学

小类 | 2 区药学

最新[2025]版：

大类 | 3 区医学

小类 | 2 区药学

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出版当年[2023]版：

Q1 PHARMACOLOGY & PHARMACY

最新[2024]版：

Q1 PHARMACOLOGY & PHARMACY

影响因子： 4.7 最新[2024版] 4.7 最新五年平均 4.2 出版当年[2023版] 4.3 出版当年五年平均 5 出版前一年[2022版] 4.7 出版后一年[2024版]

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第一作者机构： [1]Department of Cardiology & Hongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, 1111 Xianxia Road, Shanghai, 200336, China.

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