Plenary 3 Wednesday 02 June – Session 3

Gender and Cardiovascular Disease: DeLisa Fairweather, Baltimore, USA

The rise of cardiometabolic disease as global health threat: towards the UN 2030 goals

DeLisa Fairweather, PhD, is an Associate Professor of Medicine, Immunology and Clinical Translational Science at Mayo Clinic in Jacksonville, Florida and Director of Translational Research in the Department of Cardiovascular Medicine. Her research focuses on mitochondrial dynamics and the regenerative potential of extracellular vesicles to prevent cardiovascular and chronic inflammatory diseases including myocarditis. Her other research interests involve understanding the role of sex differences in promoting health and disease. She is a co-founder of the Ehlers Danlos Syndrome Clinic at Mayo Florida where she is researching the mechanisms leading to sex differences in hypermobility, and a leader of the Mayo Clinic-led US Expanded Access Program for the use of convalescent plasma for patients with COVID-19.

Cardiovascular disease characteristics differ between men and women. Observational data show that premenopausal women are protected from many cardiovascular diseases that lead to heart failure including coronary artery disease. The underlying causes of this disparity is less well understood, but may be due to tissue/organ specific effects of sex hormones. Experimental studies consistently demonstrate beneficial physiological effects of oestrogen on the vascular endothelium at cellular and molecular levels, although how depletion of oestrogen causes vascular derangement in women after the menopause is less well characterised. There is, however, emerging evidence that sex hormones alter the immune response during atherosclerosis, resulting in different disease phenotypes according to sex.

Sex hormones bind to intracellular or cell surface receptors on cardiac or immune cells, activating the regulatory element of the promoter region of specific genes and resulting in downstream effects. These regulator elements therefore represent an important cause of sex differences in gene expression. Oestrogen has been shown to have anti-inflammatory effects which may influence the immune response during the development of atherosclerosis. Sex hormones may also impact Toll-like receptors and the NLRP3 inflammasome, which are involved in regulating genes that influence the pathogenesis of immune disease. Furthermore, sex hormones may affect the process of myocardial inflammation and remodelling during myocarditis. There is also evidence to suggest that oestrogen and testosterone may have different effects on mitochondrial function and redox biology.

Understanding how inflammatory and immune mechanisms of atherosclerosis differ in men and women is critical to addressing the under-recognition and undertreatment of cardiovascular disease in women.

Recent references

Di Florio DN, Sin J, Coronado MJ, Atwal PS, Fairweather D. Sex differences in inflammation, redox biology, mitochondria and autoimmunity. Redox Biol 2020:101482.

Joyner MJ, Wright RS, Fairweather D, et al. Early safety indicators of COVID-19 convalescent plasma in 5000 patients. J Clin Invest 2020;130:4791-4797.

Coronado MJ, Bruno KA, Blauwet LA, Tschöpe C, Cunningham MW, Pankuweit S, van Linthout S, Jeon ES, McNamara DM, Krejčí J, Bienertová-Vašků J, Douglass EJ, Abston ED, Bucek A, Frisancho JA, Greenaway MS, Hill AR, Schultheiss HP, Cooper LT Jr, Fairweather D. Elevated sera sST2 is associated with heart failure in men ≤50 years old with myocarditis. J Am Heart Assoc 2019;8(2):e008968.

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