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Metabolic Heterogeneity Across Heart Failure Subtypes Defined by Integrative Multi-Omics Analysis.

Metabolic Heterogeneity Across Heart Failure Subtypes Defined by Integrative Multi-Omics Analysis.

期刊: Journal of cardiovascular translational research 日期: 2026-06-30 PMID: 42380371 DOI: 10.1007/s12265-026-10803-6 浏览: 19
作者: Xue Y, Liu L, Xu M, Jin L
Y, X., L, L., M, X., & L, J. (2026). Metabolic Heterogeneity Across Heart Failure Subtypes Defined by Integrative Multi-Omics Analysis.. Journal of cardiovascular translational research. https://doi.org/10.1007/s12265-026-10803-6
Y X, L L, M X, L J. Metabolic Heterogeneity Across Heart Failure Subtypes Defined by Integrative Multi-Omics Analysis.. Journal of cardiovascular translational research. 2026; doi: 10.1007/s12265-026-10803-6
Y X, L L, M X, et al. Metabolic Heterogeneity Across Heart Failure Subtypes Defined by Integrative Multi-Omics Analysis.[J]. Journal of cardiovascular translational research. 2026. DOI: 10.1007/s12265-026-10803-6.
@article{y2026,
  author = {Xue Y and Liu L and Xu M and Jin L},
  title = {Metabolic Heterogeneity Across Heart Failure Subtypes Defined by Integrative Multi-Omics Analysis.},
  journal = {Journal of cardiovascular translational research},
  year = {2026},
  doi = {10.1007/s12265-026-10803-6},
  note = {PMID: 42380371},
}
TY  - JOUR
AU  - Xue Y
AU  - Liu L
AU  - Xu M
AU  - Jin L
TI  - Metabolic Heterogeneity Across Heart Failure Subtypes Defined by Integrative Multi-Omics Analysis.
T2  - Journal of cardiovascular translational research
PY  - 2026
DO  - 10.1007/s12265-026-10803-6
AN  - PMID:42380371
ER  - 

摘要

Heart failure (HF) is a heterogeneous syndrome with diverse etiologies, yet the metabolic determinants specific to its subtype remain unclear. We performed an integrative multi-omics analysis combining metabolomics, genetics, and single-cell transcriptomics to characterize metabolic signatures of distinct HF subtypes. By applying Mendelian randomization of 1,091 circulating metabolites, we identified distinct metabolic patterns: lipid metabolites, particularly sphingolipids, were associated with increased HF risk, while tricarboxylic acid (TCA) cycle intermediates exhibited potential protective effects. Subtype-specific differences included lipid remodeling in coronary heart disease (CHD)-related HF, TCA metabolism in hypertension (HTN)-related HF, and amino acid pathways in overweight-related HF. Integrative analyses highlighted candidate regulators such as UPP1, NEU3, CBS, SHMT1, PLD2, OGDHL, and SULT1A1/2. Single-cell data revealed cardiomyocyte-enriched expression of OGDHL, which was consistently downregulated in experimental HF models. These findings provide insight into metabolic heterogeneity in HF and identify OGDHL as a potential regulator of cardiac metabolic remodeling.

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