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

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.