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Sex-Dependent Mechanisms of Cell Death Modalities in Cardiovascular Disease

Csaba Horvath1, Georgios Kararigas2

  • 1Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University, Bratislava, Slovak Republic.

The Canadian Journal of Cardiology
|September 24, 2022
PubMed

Insights

Biological sex significantly impacts cardiovascular disease (CVD) outcomes by influencing cell death mechanisms like pyroptosis and necroptosis. Understanding these sex-based differences, including the role of 17β-estradiol (E2), may reveal new therapeutic targets.

Area of Science:

  • Cardiovascular Biology
  • Cell Death Mechanisms
  • Sex Differences in Disease

Background:

  • Cardiovascular diseases (CVD) remain a leading global cause of mortality despite existing treatments.
  • Biological sex is a key factor influencing CVD occurrence, progression, and outcomes, yet mechanisms are not fully understood.
  • Cardiac tissue regeneration is limited, making cell death a critical contributor to irreversible damage in CVD.

Purpose of the Study:

  • To summarize current knowledge on how biological sex influences cell death mechanisms in CVD.
  • To highlight the roles of programmed necrosis-like cell death pathways, specifically pyroptosis and necroptosis.
  • To explore the inhibitory role of 17β-estradiol (E2) in these cell death pathways.

Main Methods:

  • Literature review and synthesis of existing research on sex differences in CVD.
  • Focus on apoptosis, necrosis, pyroptosis, and necroptosis in the context of CVD.
  • Analysis of the role of 17β-estradiol (E2) in modulating cell death signaling.

Main Results:

  • Biological sex significantly affects various cell death pathways implicated in CVD.
  • Pyroptosis and necroptosis are identified as crucial programmed cell death mechanisms influenced by sex.
  • 17β-estradiol (E2) demonstrates inhibitory effects on pyroptotic and necroptotic signaling pathways.

Conclusions:

  • Sex-specific mechanisms of cell death play a critical role in cardiovascular disease.
  • Targeting sex-influenced cell death pathways, particularly pyroptosis and necroptosis, offers potential therapeutic avenues.
  • Further investigation into the interplay between biological sex, E2, and cell death in CVD could lead to novel treatment strategies.

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