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Purpose <p>Myocardial infarction (MI) triggers pathological remodeling characterized by fibrosis and subsequent fibroblast-to-myofibroblast transition (FMT). Autophagy exerts a dual role in cardiac repair, balancing protective and detrimental effects. Crocetin, a carotenoid derived from saffron, exhibits anti-inflammatory and cardioprotective properties; however, its influence on autophagy-related FMT following MI remains unclear.This study aims to determine whether crocetin mitigates post-MI fibrosis and FMT by modulating autophagy in cardiac fibroblasts (CFs), while also evaluating its effects on cardiac function, infarct size, and autophagic flux.</p> Methods <p>In vivo: Mice subjected to MI were administered crocetin (25–100&#xa0;mg/kg). Cardiac function was assessed via echocardiography, and fibrosis was evaluated through Masson’s trichrome staining and immunofluorescence analysis for α-SMA/LC3. In vitro: Hypoxic CFs were treated with crocetin or the autophagy inhibitor 3-methyladenine (3-MA). The effects on autophagic flux (GFP-RFP-LC3), protein expression (Beclin-1, LC3-II/I, P62), and mitochondrial membrane potential (JC-1) were analyzed.</p> Results <p>Crocetin enhanced cardiac function, and reduced infarct size and fibrosis in a dose-dependent manner, while suppressing α-SMA expression. It promoted autophagic flux (as evidenced by increased LC3-II levels and autolysosome formation) and mitophagy (indicated by decreased mitochondrial membrane potential). Treatment with 3-MA negated the antifibrotic effects of crocetin.</p> Conclusion <p>Crocetin attenuates post-MI pathological remodeling by enhancing autophagic flux to inhibit FMT, thereby identifying it as a promising candidate for antifibrotic therapy.</p>

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Crocetin Attenuates Fibroblast-to-Myofibroblast Transition after Myocardial Infarction in Mice by Regulating Autophagy

  • 期刊论文

  • 发表日期：

    2025年8月22日

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  • Ruhui Yang,
  • Zhengyi Guo,
  • Haili Jin,
  • Chunli Liu,
  • Jia Shuo Zhao,
  • Bingjin Liu,
  • Liping Zhou,
  • Yinxiu Jin,
  • Yinping Wang,
  • Meifen Li,
  • Songquan Wu

摘要

Purpose

Myocardial infarction (MI) triggers pathological remodeling characterized by fibrosis and subsequent fibroblast-to-myofibroblast transition (FMT). Autophagy exerts a dual role in cardiac repair, balancing protective and detrimental effects. Crocetin, a carotenoid derived from saffron, exhibits anti-inflammatory and cardioprotective properties; however, its influence on autophagy-related FMT following MI remains unclear.This study aims to determine whether crocetin mitigates post-MI fibrosis and FMT by modulating autophagy in cardiac fibroblasts (CFs), while also evaluating its effects on cardiac function, infarct size, and autophagic flux.

Methods

In vivo: Mice subjected to MI were administered crocetin (25–100 mg/kg). Cardiac function was assessed via echocardiography, and fibrosis was evaluated through Masson’s trichrome staining and immunofluorescence analysis for α-SMA/LC3. In vitro: Hypoxic CFs were treated with crocetin or the autophagy inhibitor 3-methyladenine (3-MA). The effects on autophagic flux (GFP-RFP-LC3), protein expression (Beclin-1, LC3-II/I, P62), and mitochondrial membrane potential (JC-1) were analyzed.

Results

Crocetin enhanced cardiac function, and reduced infarct size and fibrosis in a dose-dependent manner, while suppressing α-SMA expression. It promoted autophagic flux (as evidenced by increased LC3-II levels and autolysosome formation) and mitophagy (indicated by decreased mitochondrial membrane potential). Treatment with 3-MA negated the antifibrotic effects of crocetin.

Conclusion

Crocetin attenuates post-MI pathological remodeling by enhancing autophagic flux to inhibit FMT, thereby identifying it as a promising candidate for antifibrotic therapy.