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A Multi-Omics Atlas of Sex-Specific Differences in Obstructive Hypertrophic Cardiomyopathy

Ramin Garmany, Surendra Dasari, J Martijn Bos

    Biorxiv : the Preprint Server for Biology
    |March 11, 2024
    PubMed

    Insights

    Sex-specific differences in hypertrophic cardiomyopathy (HCM) involve subtle multi-omics variations. This study reveals distinct molecular profiles between males and females with obstructive HCM, impacting hypertrophy pathways.

    Area of Science:

    • Cardiovascular Genetics
    • Molecular Biology
    • Genomics

    Background:

    • Hypertrophic cardiomyopathy (HCM) is a prevalent genetic heart condition.
    • Women with HCM often experience later onset but a more severe disease progression.
    • The molecular mechanisms driving these sex-based differences in HCM remain largely unknown.

    Approach:

    • RNA-sequencing, mass spectrometry-based proteomics, and phosphoproteomics were performed on cardiac tissues from 97 obstructive HCM patients and 23 controls.
    • Multi-omics data were analyzed to identify sex-specific molecular differences in HCM.
    • Comparative analysis focused on transcriptome, proteome, and phosphoproteome profiles between sexes and disease states.

    Key Points:

    • Transcriptome, proteome, and phosphoproteome profiles were largely similar between sexes in HCM, with minimal differences observed between HCM males and females.
    • Significant sex-specific differences were found in gene expression when comparing HCM patients to controls, with more differentially expressed genes in females.
    • HCM females exhibited distinct protein expression and phosphorylation patterns compared to control females, with notable hypophosphorylation and inactivation of hypertrophy pathways, contrasting with hyperphosphorylation and activation in males.

    Conclusions:

    • Subtle yet biologically significant sex-specific differences exist in the multi-omics profiles of hypertrophic cardiomyopathy.
    • This research presents a comprehensive atlas of sex-specific variations in the transcriptome, proteome, and phosphoproteome in obstructive HCM.
    • Understanding these molecular distinctions is crucial for elucidating the sex-based disparities in HCM severity and progression.
    Abstract

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