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Background <p>Clinical studies have demonstrated that multiple inflammatory related proteins are associated with hypertrophic cardiomyopathy (HCM). However, the precise role of these factors in the pathogenesis of HCM remains uncertain.</p> Methods <p>The link between inflammatory related proteins and HCM was analyzed using Mendelian randomization (MR), followed by bioinformatics to explore the role of inflammatory related proteins in HCM. In vivo and in vitro models of HCM were established to elucidate how inflammatory related proteins influence HCM progression.</p> Results <p>Our MR analysis revealed a negative correlation between the inflammation related protein CX3CL1 and HCM. Bioinformatics and in vivo data similarly demonstrated a reduction in CX3CL1 expression in HCM. CX3CL1 was found to be mainly expressed in cardiomyocytes and endothelial cells via the Human Protein Atlas database and its’ expression in both cells was obviously downregulated after being treated by angiotensin-II. Importantly, functional characteristics and correlation analysis of CX3CL1 indicated that it was most closely associated with macrophages efferocytosis. Consequently, we examined the signature molecules (AXL, MERTK, and TYRO3) associated with efferocytosis, which revealed a significant decrease in their expression in HCM. Notably, recombinant mouse CX3CL1 (rm-CX3CL1) reversed this process.</p> Conclusions <p>In conclusion, CX3CL1-meidated impaired efferocytosis plays a critical role in the initiation and development of HCM, and modulation of CX3CL1 may prove advantageous in managing HCM progression.</p>

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Impaired endothelial cell-derived CX3CL1-mediated macrophage efferocytosis in hypertrophic cardiomyopathy based on multi-omics analysis

  • 期刊论文

  • 发表日期：

    2025年8月5日

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  • Yan Zhang,
  • Xin Yan,
  • Xiao-lei Fu,
  • Hai-bing Yang,
  • Yi-min Yan,
  • He-fan He,
  • Li Yang

摘要

Background

Clinical studies have demonstrated that multiple inflammatory related proteins are associated with hypertrophic cardiomyopathy (HCM). However, the precise role of these factors in the pathogenesis of HCM remains uncertain.

Methods

The link between inflammatory related proteins and HCM was analyzed using Mendelian randomization (MR), followed by bioinformatics to explore the role of inflammatory related proteins in HCM. In vivo and in vitro models of HCM were established to elucidate how inflammatory related proteins influence HCM progression.

Results

Our MR analysis revealed a negative correlation between the inflammation related protein CX3CL1 and HCM. Bioinformatics and in vivo data similarly demonstrated a reduction in CX3CL1 expression in HCM. CX3CL1 was found to be mainly expressed in cardiomyocytes and endothelial cells via the Human Protein Atlas database and its’ expression in both cells was obviously downregulated after being treated by angiotensin-II. Importantly, functional characteristics and correlation analysis of CX3CL1 indicated that it was most closely associated with macrophages efferocytosis. Consequently, we examined the signature molecules (AXL, MERTK, and TYRO3) associated with efferocytosis, which revealed a significant decrease in their expression in HCM. Notably, recombinant mouse CX3CL1 (rm-CX3CL1) reversed this process.

Conclusions

In conclusion, CX3CL1-meidated impaired efferocytosis plays a critical role in the initiation and development of HCM, and modulation of CX3CL1 may prove advantageous in managing HCM progression.