Large-scale in silico identification of drugs exerting sex-specific effects in the heart

Journal of Translational Medicine
Changting CuiQinghua Cui

Abstract

Major differences exist between men and women in both physiology and pathophysiology. Dissecting the underlying processes and contributing mechanisms of sex differences in health and disease represents a crucial step towards precision medicine. Considering the significant differences between men and women in the response to pharmacotherapies, our aim was to develop an in silico model able to predict sex-specific drug responses in a large-scale. For this purpose, we focused on cardiovascular effects because of their high morbidity and mortality. Our model predicted several drugs (including acebutolol and tacrine) with significant differences in the heart between men and women. To validate the sex-specific drug responses identified by our model, acebutolol was selected to lower blood pressure in spontaneous hypertensive rats (SHR), tacrine was used to assess cardiac injury in mice and metformin as control for a non-sex-specific response. As our model predicted, acebutolol exhibited a stronger decrease in heart rate and blood pressure in female than male SHRs. Tacrine lowered heart rate in male but not in female mice, induced higher plasma cTNI level and increased cardiac superoxide (DHE staining) generation in female than male mi...Continue Reading

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Citations

Oct 10, 2018·American Journal of Hypertension·Lindsey A Ramirez, Jennifer C Sullivan
Dec 22, 2019·British Journal of Pharmacology·Marisol Ruiz-MeanaKirsti Ytrehus
Dec 7, 2019·International Journal of Molecular Sciences·Lukas AltinbasGeorgios Kararigas
Jun 4, 2020·Biology of Sex Differences·Andrea Rodrigues Sabbatini, Georgios Kararigas
Mar 7, 2020·Journal of the American College of Cardiology·Andrea Rodrigues Sabbatini, Georgios Kararigas

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Methods Mentioned

BETA
pharmacotherapies
ELISA

Software Mentioned

SexBiasedDrug Map
Connectivity Map
R
Java
SexBiasedDrug
Powerlab

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