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<p>Myocardial fibrosis is a pivotal pathological process driving the progression of cardiovascular disease, with myofibroblasts originating from endothelial-to-mesenchymal transition (EndMT) playing a central role in fibrotic remodeling. However, current therapeutic strategies remain suboptimal, exhibiting significant limitations in clinical application and failing to adequatelyaddress the treatment demands of myocardial fibrosis. In this study, we developed an innovative injectable hydrogel, Scu@PUE, endowed with EndMT-modulating properties. This hydrogel was precisely engineered through the spontaneous supramolecular assembly of Puerarin (PUE) and Scutellarin (Scu) under strictly regulated thermodynamic conditions, ensuring structural stability and biological functionality. To comprehensively assess its therapeutic potential, we conducted systematic <i>in vivo</i> and <i>in vitro</i> evaluations to elucidate the mechanistic role of Scu@PUE in suppressing EndMT and ameliorating myocardial fibrosis. Experimental findings demonstrated that Scu@PUE exhibits an optimized spatial architecture, while molecular dynamics simulations further revealed a stable and efficient intermolecular interaction between PUE and Scu. Pharmacodynamic analyses confirmed the significant therapeutic efficacy of Scu@PUE in the treatment of myocardial fibrosis, particularly in an isoproterenol (ISO)-induced murine model of cardiac dysfunction. Scu@PUE administration effectively enhanced cardiac ejection fraction improved ventricular wall thickness, and markedly alleviated fibrosis-associated pathological manifestations. Furthermore, mechanistic investigations indicated that Scu@PUE treatment significantly attenuated EndMT during myocardial fibrosis progression. This regulatory effect was found to be mediated, at least in part, via suppression of the IFN-γ-STAT1 signaling axis, thereby mitigating EndMT-driven pathological remodeling. In conclusion, this study introduces a novel EndMT-targeted therapeutic strategy based on the precisely designed injectable hydrogel Scu@PUE, offering a promising approach for the treatment of myocardial fibrosis with potential translational implications in clinical applications.</p>

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Injectable hydrogel with vascular regulatory properties ameliorates myocardial fibrosis via suppressing endothelial-to-mesenchymal transition

  • 期刊论文

  • 发表日期：

    2026年4月27日

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  • Xingwang Cao,
  • Rui Zeng,
  • Mingyue Yao,
  • Bo Li,
  • Wenjun Miao,
  • Hao Feng,
  • Shan Li,
  • Qingrong Pu,
  • Yuan Yuan,
  • Li Dong,
  • Rui Huang

摘要

Myocardial fibrosis is a pivotal pathological process driving the progression of cardiovascular disease, with myofibroblasts originating from endothelial-to-mesenchymal transition (EndMT) playing a central role in fibrotic remodeling. However, current therapeutic strategies remain suboptimal, exhibiting significant limitations in clinical application and failing to adequatelyaddress the treatment demands of myocardial fibrosis. In this study, we developed an innovative injectable hydrogel, Scu@PUE, endowed with EndMT-modulating properties. This hydrogel was precisely engineered through the spontaneous supramolecular assembly of Puerarin (PUE) and Scutellarin (Scu) under strictly regulated thermodynamic conditions, ensuring structural stability and biological functionality. To comprehensively assess its therapeutic potential, we conducted systematic in vivo and in vitro evaluations to elucidate the mechanistic role of Scu@PUE in suppressing EndMT and ameliorating myocardial fibrosis. Experimental findings demonstrated that Scu@PUE exhibits an optimized spatial architecture, while molecular dynamics simulations further revealed a stable and efficient intermolecular interaction between PUE and Scu. Pharmacodynamic analyses confirmed the significant therapeutic efficacy of Scu@PUE in the treatment of myocardial fibrosis, particularly in an isoproterenol (ISO)-induced murine model of cardiac dysfunction. Scu@PUE administration effectively enhanced cardiac ejection fraction improved ventricular wall thickness, and markedly alleviated fibrosis-associated pathological manifestations. Furthermore, mechanistic investigations indicated that Scu@PUE treatment significantly attenuated EndMT during myocardial fibrosis progression. This regulatory effect was found to be mediated, at least in part, via suppression of the IFN-γ-STAT1 signaling axis, thereby mitigating EndMT-driven pathological remodeling. In conclusion, this study introduces a novel EndMT-targeted therapeutic strategy based on the precisely designed injectable hydrogel Scu@PUE, offering a promising approach for the treatment of myocardial fibrosis with potential translational implications in clinical applications.