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<p>Heart failure (HF) represents the final stage of cardiovascular disease progression, characterized by high morbidity and mortality. Pressure overload in HF activates the PI3K/AKT pathway, and prolonged activation leads to pathological cardiac hypertrophy. However, the mechanism underlying sustained PI3K/AKT activation in pressure overload-induced HF remains unclear. In this study, we demonstrate that miR-203 overexpression in transgenic mice counteracts cardiac dysfunction and pathological remodeling in HF, whereas miR-203 downregulation exacerbates HF. At the cellular level, miR-203 overexpression significantly reduces Angiotensin II (Ang II)-induced cardiomyocyte hypertrophy and injury, while miR-203 knockdown aggravates these effects. Mechanistically, miR-203 binds to the 3’ untranslated region (3’UTR) of insulin-like growth factor binding protein 5 (IGFBP5) mRNA, inhibiting IGFBP5 protein expression, thereby suppressing PI3K/AKT signaling and mitigating cardiomyocyte hypertrophy. Furthermore, we demonstrate that fibronectin-1 (FN1) is a critical functional partner for IGFBP5, as knockdown of FN1 attenuates IGFBP5-induced PI3K/AKT activation and hypertrophy. This study is the first to elucidate the role and mechanism of miR-203 in regulating pressure overload-induced HF, offering a potential genetic tool for HF therapy.</p><p></p>

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miR-203 improves pressure overload-induced heart failure by targeting the IGFBP5/PI3K/AKT axis

  • 期刊论文

  • 发表日期：

    2026年8月4日

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  • Ping-ping Tang,
  • Run Xu,
  • Song Wang,
  • Wei-yi Zhang,
  • Xin-xin Dong,
  • Li-na Yao,
  • Ling-yi Kong,
  • Chang Mao,
  • Yu-dong Bao,
  • Hui-qian Tang,
  • Dian-ya Sun,
  • Ning Wang,
  • Xin Liu,
  • Yong Zhang

摘要

Heart failure (HF) represents the final stage of cardiovascular disease progression, characterized by high morbidity and mortality. Pressure overload in HF activates the PI3K/AKT pathway, and prolonged activation leads to pathological cardiac hypertrophy. However, the mechanism underlying sustained PI3K/AKT activation in pressure overload-induced HF remains unclear. In this study, we demonstrate that miR-203 overexpression in transgenic mice counteracts cardiac dysfunction and pathological remodeling in HF, whereas miR-203 downregulation exacerbates HF. At the cellular level, miR-203 overexpression significantly reduces Angiotensin II (Ang II)-induced cardiomyocyte hypertrophy and injury, while miR-203 knockdown aggravates these effects. Mechanistically, miR-203 binds to the 3’ untranslated region (3’UTR) of insulin-like growth factor binding protein 5 (IGFBP5) mRNA, inhibiting IGFBP5 protein expression, thereby suppressing PI3K/AKT signaling and mitigating cardiomyocyte hypertrophy. Furthermore, we demonstrate that fibronectin-1 (FN1) is a critical functional partner for IGFBP5, as knockdown of FN1 attenuates IGFBP5-induced PI3K/AKT activation and hypertrophy. This study is the first to elucidate the role and mechanism of miR-203 in regulating pressure overload-induced HF, offering a potential genetic tool for HF therapy.