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Sex-Specific Human Cardiomyocyte Gene Regulation in Left Ventricular Pressure Overload.

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Gene expression in male patients with aortic stenosis showed higher levels of structural and inflammation-related genes, impacting cardiac function differently than in female patients. These findings highlight sex-specific differences in pressure overload responses.

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Area of Science:

  • Cardiovascular Biology
  • Molecular Cardiology
  • Genomics

Background:

  • Aortic stenosis (AS) is a significant cardiovascular condition.
  • Sex-based differences in cardiovascular disease progression and response to therapy are increasingly recognized.
  • Understanding cardiomyocyte-specific molecular changes in AS is crucial for targeted treatment.

Purpose of the Study:

  • To investigate sex-based differences in gene expression within cardiomyocytes from patients with aortic stenosis.
  • To test the hypothesis that maladaptive remodeling and inflammation-related genes are upregulated in male versus female AS patients.
  • To explore the relationship between specific genes, cardiac function, and sex in AS.

Main Methods:

  • Gene expression analysis of cardiomyocytes isolated from the interventricular septum of 34 patients undergoing aortic valve replacement.
  • Collection of pre-operative clinical and echocardiographic data.
  • Comparative analysis of gene expression and cardiac parameters between male and female patient cohorts.

Main Results:

  • Male patients exhibited increased left ventricular end-diastolic diameter and posterior wall thickness, with lower ejection fraction compared to females.
  • Most structural genes involved in cardiac hypertrophy and remodeling were expressed at higher levels in males.
  • Two inflammation-related genes, CCN2 and NFKB1, showed a male-specific negative association with ejection fraction.

Conclusions:

  • Novel insights into cardiomyocyte-specific molecular alterations driven by sex differences in pressure overload.
  • A significant male-specific link between cardiac function and inflammation-related genes in aortic stenosis.
  • Emphasizing sex differences in research and therapeutic strategies for aortic stenosis is essential for personalized medicine.