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<p>Latent transforming growth factor β-binding protein 4 (LTBP4) has been reported to be associated with heart failure (HF), but its role in HF remains unclear. We observe increased LTBP4 expression in plasma and cardiomyocytes of HF patients, and in a male mouse HF model induced by transverse aortic constriction (TAC). Cardiomyocyte-specific <i>Ltbp4</i> deficiency attenuates NLRP3 inflammasome activation, cardiac dysfunction, and fibrosis post-TAC. Mechanistically, pressure overload upregulates LTBP4 partially via the transcription factor SP1. Angiotensin II promotes the recruitment of intracellular LTBP4 to the microtubule-organizing center (MTOC) via dynein. Subsequently, LTBP4 facilitates the dynein-mediated NLRP3 translocation to the MTOC and promotes NLRP3-NEK7 interaction, thereby driving NLRP3 inflammasome activation. Additionally, LTBP4 upregulates NLRP3 transcription and correlates positively with NLRP3 and interleukin-1β in HF patients. Here we show that LTBP4 is an important regulator of the NLRP3-NEK7 interaction and NLRP3 inflammasome activation in cardiomyocytes, highlighting its potential as a therapeutic target for HF.</p>

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LTBP4 deficiency inhibits NLRP3 inflammasome activation in cardiomyocytes and attenuates heart failure in male mice

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月15日

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  • Siyu Ma,
  • Nan Jiang,
  • Zheng Zuo,
  • Zhipeng Lian,
  • Jian Wu,
  • Jinghua Ma,
  • Xiangxiang Wei,
  • Yunquan He,
  • Qi Pan,
  • Jiayi Lin,
  • Yongbo Li,
  • Yannan Hou,
  • Xiuling Zhi,
  • Xiaobo Li,
  • Elena Osto,
  • Yuxiang Dai,
  • Jun Li,
  • Jieyu Guo,
  • Dan Meng

摘要

Latent transforming growth factor β-binding protein 4 (LTBP4) has been reported to be associated with heart failure (HF), but its role in HF remains unclear. We observe increased LTBP4 expression in plasma and cardiomyocytes of HF patients, and in a male mouse HF model induced by transverse aortic constriction (TAC). Cardiomyocyte-specific Ltbp4 deficiency attenuates NLRP3 inflammasome activation, cardiac dysfunction, and fibrosis post-TAC. Mechanistically, pressure overload upregulates LTBP4 partially via the transcription factor SP1. Angiotensin II promotes the recruitment of intracellular LTBP4 to the microtubule-organizing center (MTOC) via dynein. Subsequently, LTBP4 facilitates the dynein-mediated NLRP3 translocation to the MTOC and promotes NLRP3-NEK7 interaction, thereby driving NLRP3 inflammasome activation. Additionally, LTBP4 upregulates NLRP3 transcription and correlates positively with NLRP3 and interleukin-1β in HF patients. Here we show that LTBP4 is an important regulator of the NLRP3-NEK7 interaction and NLRP3 inflammasome activation in cardiomyocytes, highlighting its potential as a therapeutic target for HF.