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<p>Hypertrophic cardiomyopathy (HCM) is the most common genetic myocardial disease, characterized by asymmetric left ventricular hypertrophy (LVH) due to sarcomeric mutations. Aortic stenosis (AS) results in concentric LVH, due to pressure overload. The aim of this study was to identify signaling pathways differentially regulated in HCM compared to AS, using plasma proteomic profiling. 76 HCM cases and 36 AS controls were matched by age and sex. A machine-learning (ML) model to predict HCM was built in the training set (70% cohort) and examined in the test set (30% cohort). Pathway analysis of proteins differentially expressed between HCM and AS was performed. The ML model accurately distinguished HCM from AS, with area under the receiver&#xa0;operating&#xa0;characteristic curve of 0.90 (95% CI: 0.79–1.00). Pathway analysis revealed differential regulation of Ras-MAPK, inflammatory and metabolic pathways. In conclusion, this study identified distinctive proteomic profiles and signaling pathways underlying LVH in HCM compared to AS.</p> Graphical Abstract <p>Comprehensive plasma proteomic profiling enables identification of distinctive proteomic profiles and signaling pathways underlying left ventricular hypertrophy in hypertrophic cardiomyopathy compared to aortic stenosis.</p> <p></p>

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Comprehensive Plasma Proteomic Profiling Reveals Differentially Regulated Signaling Pathways Underlying Left Ventricular Hypertrophy Between Hypertrophic Cardiomyopathy and Aortic Stenosis

  • 期刊论文

  • 发表日期：

    2025年4月14日

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  • Heidi S. Lumish,
  • Lorenzo R. Sewanan,
  • Lusha W. Liang,
  • Kohei Hasegawa,
  • Mathew S. Maurer,
  • Muredach P. Reilly,
  • Yuichi J. Shimada

摘要

Hypertrophic cardiomyopathy (HCM) is the most common genetic myocardial disease, characterized by asymmetric left ventricular hypertrophy (LVH) due to sarcomeric mutations. Aortic stenosis (AS) results in concentric LVH, due to pressure overload. The aim of this study was to identify signaling pathways differentially regulated in HCM compared to AS, using plasma proteomic profiling. 76 HCM cases and 36 AS controls were matched by age and sex. A machine-learning (ML) model to predict HCM was built in the training set (70% cohort) and examined in the test set (30% cohort). Pathway analysis of proteins differentially expressed between HCM and AS was performed. The ML model accurately distinguished HCM from AS, with area under the receiver operating characteristic curve of 0.90 (95% CI: 0.79–1.00). Pathway analysis revealed differential regulation of Ras-MAPK, inflammatory and metabolic pathways. In conclusion, this study identified distinctive proteomic profiles and signaling pathways underlying LVH in HCM compared to AS.

Graphical Abstract

Comprehensive plasma proteomic profiling enables identification of distinctive proteomic profiles and signaling pathways underlying left ventricular hypertrophy in hypertrophic cardiomyopathy compared to aortic stenosis.