Sex differences in inflammation during atherosclerosis

Area of Science:

• Cardiovascular Science
• Immunology
• Sex Differences in Disease

Background:

• Atherosclerosis is a major global cause of mortality, with notable sex-based disparities in incidence and age of onset.
• Women often develop atherosclerosis post-menopause, especially with autoimmune conditions, suggesting sex-specific immune pathways.
• Key pathogenic processes include vascular inflammation, lipid accumulation, fibrosis, and plaque instability leading to ischemic events.

Purpose of the Study:

• To review current knowledge on sex differences in the inflammatory immune response during atherosclerosis.
• To highlight how sex hormones influence immune responses and disease phenotypes.
• To underscore the importance of sex as a biological variable in understanding cardiovascular disease.

Main Methods:

• Literature review of studies investigating sex differences in atherosclerosis pathogenesis.
• Analysis of research on immune mechanisms, including innate and adaptive immunity, in relation to sex hormones.
• Synthesis of evidence on differential immune responses to infection and damage between sexes.

Main Results:

• Men exhibit elevated innate immune activation in atherosclerosis.
• Women show increased antibody and autoantibody responses, particularly post-menopause and with autoimmune diseases.
• Sex hormones significantly modulate immune responses, leading to distinct atherosclerosis phenotypes in men and women.

Conclusions:

• Significant sex differences exist in the inflammatory immune response underlying atherosclerosis.
• These disparities contribute to different disease manifestations and outcomes between men and women.
• Recognizing and understanding these sex-specific immune mechanisms is essential for advancing precision medicine in cardiovascular disease treatment.