{
  "abstract": "Background: Rheumatic heart disease (RHD) is characterized by persistent valvular inflammation and fibrosis. Lactate-driven lysine lactylation may couple metabolic stress to inflammatory transcription, but its relationship with CXCL12-mediated immune recruitment in RHD valves remains unclear.\n\nMethods: Paired aortic and mitral valve single-cell RNA-sequencing data from three patients with RHD were analyzed, yielding 47,237 quality-controlled cells. CXCL12-producing cell populations were identified, and lactylation-related transcriptional states and inflammatory pathways were assessed in CXCL12-high structural cells using complementary scoring and pseudobulk approaches. CellChat was used to infer CXCL12-mediated intercellular communication, with GSE153555 used for external validation. Human valve interstitial cells (VICs) were treated with lactate, the p300 inhibitor A-485, or the NF-κB inhibitor BAY 11-7082. CXCL12/CXCR4-dependent monocyte chemotaxis was evaluated using THP-1 cells, AMD3100, and a CXCL12-neutralizing antibody.\n\nResults: VICs and myofibroblasts were the principal CXCL12-producing cells. Within CXCL12-high structural cells, a higher lactylation-related transcriptional state was associated with enhanced NF-κB and TNF signaling and increased IL6, BIRC3, REL, and TNFAIP3 expression. CellChat supported CXCL12-CXCR4 communication from structural cells to myeloid and lymphoid cells, while external validation confirmed increased CXCL12, IL6, and TNFAIP3 expression in diseased valves. In VICs, lactate increased Pan-Kla, H3K9la, H3K14la, and CXCL12 expression and secretion. A-485 attenuated lactylation-associated CXCL12 induction, whereas BAY 11-7082 suppressed NF-κB activation and CXCL12 expression. Lactate-conditioned medium enhanced THP-1 migration and inflammatory gene expression, which were reduced by pathway inhibition or CXCL12/CXCR4 blockade.\n\nConclusion: These findings link lactylation-associated metabolic signaling in RHD valve structural cells to NF-κB-dependent CXCL12 production and CXCL12-CXCR4-mediated monocyte recruitment, providing a mechanistic framework for stromal–immune communication in RHD.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Cardiac Surgery, Zhongshan Hospital Fudan University, 180 Fenglin Road, Shanghai, 200032, China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Junyu Zhai"
    },
    {
      "affs": [
        0
      ],
      "name": "Zheng Zuo"
    },
    {
      "affs": [
        0
      ],
      "name": "Tao Yan"
    },
    {
      "affs": [
        0
      ],
      "name": "Fangyu Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Jiaxing Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Kai Zhu"
    },
    {
      "affs": [
        0
      ],
      "name": "Hao Lai"
    },
    {
      "affs": [
        0
      ],
      "name": "Chunsheng Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Jun Li"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ez2qsq9j4b6hx.bib",
  "cited_by": 0,
  "doi": "10.1016/j.jtauto.2026.100405",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13734818/",
  "id": "ez2qsq9j4b6hx",
  "issns": [
    "2589-9090"
  ],
  "landing_url": "https://doi.org/10.1016/j.jtauto.2026.100405",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research paper"
    ],
    [
      "openalex",
      "2725|Streptococcal Infections and Treatments"
    ]
  ],
  "openalex": "W7221610441",
  "pdf_url": null,
  "pmcid": "PMC13734818",
  "pmid": "42990878",
  "published": "2026-10-13",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/ez2qsq9j4b6hx.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T12:20:38Z",
      "native_id": "PMC13734818",
      "source": "pmc",
      "url": "https://doi.org/10.1016/j.jtauto.2026.100405"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2725|Streptococcal Infections and Treatments",
      "subfield": "infectious-disease"
    }
  ],
  "title": "Lactylation-associated CXCL12-mediated intercellular communication in rheumatic heart disease valves",
  "title_text": "Lactylation-associated CXCL12-mediated intercellular communication in rheumatic heart disease valves",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T12:20:38Z",
  "url": "https://research.draconitic.com/paper/ez2qsq9j4b6hx",
  "venue": "Journal of Translational Autoimmunity",
  "versions": []
}