{
  "abstract": "Background: Although metabolic reprogramming has attracted growing attention in hypertrophic cardiomyopathy (HCM), transcriptomic and proteomic studies have yielded conflicting views on glycolytic alterations. As a master transcriptional regulator of glycolytic genes, HIF1α remains poorly characterized in human HCM tissue.\n\nMethods: We integrated four transcriptomic datasets, three proteomic datasets, and one phosphoproteomic dataset from publicly available human HCM cohorts. Glycolysis-, hypoxia-, and oxidative metabolism-related pathways were assessed by gene set enrichment analysis (GSEA). Transcript-protein concordance was evaluated by comparing the direction and magnitude of individual glycolytic enzyme changes across omics layers.\n\nResults: Across all four transcriptomic cohorts, glycolysis-related programs were suppressed at the mRNA level (NES range: −1.1 to −1.7). HALLMARK_HYPOXIA was negatively enriched in four of five transcriptomic comparisons, and Semenza HIF1 targets showed the strongest suppression (NES = −1.99, P adj = 2.8 × 10 ⁻⁴ ). At the protein level, alterations differed by pathway. Oxidative pathways (OXPHOS, TCA cycle, FAO) showed concordant downregulation at RNA and protein levels, whereas glycolytic enzymes displayed level-specific discordance. In Garmany 2023 paired samples, 5 of 12 glycolytic enzymes showed opposite RNA and protein directions, whereas the overall RNA–protein correlation was weak and non-significant ( r = −0.28, P = 0.38; n = 12) and was therefore considered descriptive. HK1 was the most prominent example of transcript-proteome decoupling, with reduced transcripts in four transcriptomic cohorts but increased protein levels across three independent proteomic platforms (Garmany TMT, Nollet LC-MS/MS, Lumish SomaScan). GSEA in Garmany 2023 demonstrated opposite enrichment patterns between transcriptome and proteome for Glycolysis (NES −1.11 vs. +1.40) and Hypoxia (NES −1.89, P adj < 0.001 vs. +1.34, ns), although proteomic enrichment did not reach FDR significance. Phosphoproteomic analysis revealed enzyme-specific rather than pathway-wide changes: HK1 (log2FC + 0.18, FDR < 10 ⁻⁵ ) and PGAM1 (+0.40, FDR = 0.02) showed increased phosphorylation, whereas ALDOA, LDHB, PKM, and PFKM showed decreased phosphorylation (all FDR < 0.01).\n\nConclusions: Our study identifies a transcript-protein disconnect in glycolytic metabolism in human HCM. HIF1-associated transcriptional programs were reduced rather than activated. Oxidative pathways (OXPHOS, TCA cycle, FAO) showed coordinated downregulation across RNA and protein levels, whereas glycolysis exhibited frequent RNA-protein divergence, suggesting distinct regulatory mechanisms across metabolic pathways in HCM.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Cardiovascular Medicine, The Second Xiangya Hospital of Central South University",
    "Department of Cardiovascular Medicine, Guilin Hospital of the Second Xiangya Hospital, Central South University"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Jingyuan Chen"
    },
    {
      "affs": [
        0
      ],
      "name": "Die Hu"
    },
    {
      "affs": [
        0
      ],
      "name": "Yang Yang"
    },
    {
      "affs": [
        0
      ],
      "name": "Mingqi Ouyang"
    },
    {
      "affs": [
        1
      ],
      "name": "Xiaoman Chen"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/f00r66f9tqqpy.bib",
  "cited_by": 0,
  "doi": "10.3389/fcvm.2026.1937619",
  "fulltext_url": null,
  "id": "f00r66f9tqqpy",
  "issns": [
    "2297-055X"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fcvm.2026.1937619/full",
  "language": null,
  "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": [
    [
      "openalex",
      "2705|Cardiomyopathy and Myosin Studies"
    ]
  ],
  "openalex": "W7223125270",
  "pdf_url": "https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2026.1937619/pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-21",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/f00r66f9tqqpy.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:10Z",
      "native_id": "10.3389/fcvm.2026.1937619",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fcvm.2026.1937619/full"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2705|Cardiomyopathy and Myosin Studies",
      "subfield": "cardiovascular"
    }
  ],
  "title": "Selective transcript–protein discordance of glycolytic remodeling in human hypertrophic cardiomyopathy",
  "title_text": "Selective transcript–protein discordance of glycolytic remodeling in human hypertrophic cardiomyopathy",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:10Z",
  "url": "https://research.draconitic.com/paper/f00r66f9tqqpy",
  "venue": "Frontiers in Cardiovascular Medicine",
  "versions": []
}