Identification and validation of differentially expressed disulfidptosis-related genes in hypertrophic cardiomyopathy

Huimin Fan1, Xin Tan2,3, Shuai Xu2,3

  • 1Center of Translational Medicine and Clinical Laboratory, Suzhou Dushu Lake Hospital, The Fourth Affiliated Hospital to Soochow University, Suzhou, 215000, China.

PubMed

Insights

This study explores disulfidptosis, a novel cell death mechanism, in hypertrophic cardiomyopathy (HCM). Researchers developed a predictive model using disulfidptosis-related genes for potential HCM biomarkers and therapeutic targets.

Area of Science:

  • Cardiovascular Research
  • Cell Death Mechanisms
  • Biomarker Discovery

Background:

  • Hypertrophic cardiomyopathy (HCM) is a prevalent cardiovascular disease with complex origins and limited treatment options.
  • Disulfidptosis, a recently identified form of programmed cell death, has been primarily investigated in cancer, with its role in cardiovascular diseases largely unexplored.

Purpose of the Study:

  • To investigate the potential association between disulfidptosis and the pathogenesis of hypertrophic cardiomyopathy.
  • To develop a predictive model for HCM utilizing genes associated with disulfidptosis.
  • To identify potential therapeutic strategies targeting disulfidptosis pathways in HCM.

Main Methods:

  • Development of a predictive model using Support Vector Machine (SVM) machine learning.
  • Identification of key disulfidptosis-related genes (DRGs) including GYS1, MYH10, PDMIL1, SLC3A2, and CAPZB.
  • Validation of findings in a Transverse Aortic Constriction (TAC) mouse model using western blot, RNA sequencing, and immunohistochemistry.
  • Utilized the Comparative Toxicogenomics Database (CTD) to identify potential therapeutic agents.

Main Results:

  • A predictive model incorporating specific DRGs demonstrated high performance in identifying HCM.
  • The study validated the presence and relevance of disulfidptosis-associated genes in a mouse model of cardiac hypertrophy.
  • Resveratrol was identified as a potential therapeutic agent targeting core genes involved in disulfidptosis within the context of HCM.

Conclusions:

  • Disulfidptosis represents a novel area of investigation for understanding hypertrophic cardiomyopathy.
  • The identified DRGs and the predictive model offer promising avenues for biomarker discovery in HCM.
  • Resveratrol emerges as a potential therapeutic candidate for targeting disulfidptosis in hypertrophic cardiomyopathy, warranting further clinical investigation.