{
  "abstract": "Myocardial infarction (MI) triggers persistent inflammatory dysregulation, wherein macrophages undergo glycolytic reprogramming and adopt an inflammatory phenotype that impairs cardiac repair. However, the specific metabolic drivers underlying post-MI macrophage dysfunction remain unclear. Here, we identify enolase 1 (ENO1)-a glycolytic enzyme up-regulated in post-MI macrophages-as a critical regulator of macrophage metabolic fate and inflammatory function. To intervene, we engineered an acid-responsive nanocarrier (PECS) that externalizes phosphatidylserine within the acidic infarct microenvironment, facilitating selective macrophage uptake. Intracellular delivery of siENO1 suppressed glycolytic flux, thereby curbing lactate accumulation and relieving its metabolic inhibition of KLF4, which initiated anti-inflammatory reprogramming. In vivo, PECS-loaded siENO1 (siENO1@PECS) treatment attenuated infarct size, fibrosis, and cardiomyocyte apoptosis while improving ventricular function. Collectively, these findings identify ENO1 as a critical metabolic checkpoint in post-MI macrophage regulation and demonstrate a bioresponsive nanocarrier strategy for precise gene modulation to enhance cardiac repair.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Cardiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.",
    "Institute of Cardiovascular Disease Research, Xuzhou Medical University, Xuzhou, Jiangsu, China.",
    "Jiangsu Province Key Laboratory in Anesthesiology and Brain Science, Xuzhou Medical University, Xuzhou, Jiangsu, China.",
    "Department of Cardiology, Huashan Hospital, Fudan University, Shanghai, China.",
    "School of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu, China.",
    "Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu, China.",
    "Internal Medicine Department, Richmond University Medical Center, 355 Bard Ave, Staten Island, NY, USA.",
    "The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China."
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Ruoshui Li",
      "orcid": "0000-0003-3922-686X"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Gaoyang Li",
      "orcid": "0009-0003-8744-9934"
    },
    {
      "affs": [
        2,
        4,
        5
      ],
      "name": "Jie Li",
      "orcid": "0000-0001-5992-3094"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Zekun Lou"
    },
    {
      "affs": [
        2,
        4,
        5
      ],
      "name": "Xuerou Jin"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Jun Yan"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Hongping Chen"
    },
    {
      "affs": [
        6
      ],
      "name": "Fang Zhang"
    },
    {
      "affs": [
        2,
        4,
        5,
        7
      ],
      "name": "Xiaoran Deng",
      "orcid": "0009-0009-3056-5292"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Tongda Xu",
      "orcid": "0000-0002-5594-3992"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0f1dr38x35f8k.bib",
  "cited_by": 0,
  "doi": "10.1126/sciadv.aeg3270",
  "fulltext_url": null,
  "id": "0f1dr38x35f8k",
  "issns": [
    "2375-2548"
  ],
  "landing_url": "https://www.science.org/doi/10.1126/sciadv.aeg3270",
  "language": null,
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2705|Cardiac Fibrosis and Remodeling"
    ]
  ],
  "openalex": "W7215850811",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-02",
  "publisher": "American Association for the Advancement of Science (AAAS)",
  "ris": "https://research.draconitic.com/paper/0f1dr38x35f8k.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:41Z",
      "native_id": "10.1126/sciadv.aeg3270",
      "source": "crossref",
      "url": "https://www.science.org/doi/10.1126/sciadv.aeg3270"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2705|Cardiac Fibrosis and Remodeling",
      "subfield": "cardiovascular"
    }
  ],
  "title": "Targeting the ENO1 metabolic checkpoint via microenvironment-responsive nanotherapeutics promotes postinfarction cardiac repair",
  "title_text": "Targeting the ENO1 metabolic checkpoint via microenvironment-responsive nanotherapeutics promotes postinfarction cardiac repair",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:41Z",
  "url": "https://research.draconitic.com/paper/0f1dr38x35f8k",
  "venue": "Science Advances",
  "versions": []
}