Sex in cardiovascular disease: Why this biological variable should be considered in in vitro models

Area of Science:

• Cardiovascular Science
• Sex Differences Research
• Preclinical Models

Background:

• Cardiovascular disease (CVD) is a leading global cause of mortality with significant sex-based disparities.
• Cardiovascular sexual dimorphism underlies many observed epidemiological and clinical differences between sexes.
• Current in vitro models for CVD research often lack sex reporting and exhibit a male bias, questioning their biological relevance.

Purpose of the Study:

• To highlight the critical role of sex as a biological variable (SABV) in cardiovascular (patho)physiology.
• To review current limitations in SABV practices within CVD preclinical research.
• To advocate for the routine inclusion of SABV in in vitro CVD models for equitable patient treatment.

Main Methods:

• Discussion of the role of sex in CVD and cardiovascular pathophysiology.
• Review of existing SABV practices and their shortcomings.
• Exploration of emerging strategies for SABV integration in primary cell, stem cell, and 3D in vitro models.

Main Results:

• Identified significant shortcomings in current SABV reporting and implementation in CVD research.
• Highlighted the necessity of sex-specific in vitro models to accurately reflect disease biology.
• Presented strategies for incorporating SABV across diverse in vitro model systems.

Conclusions:

• The consistent inclusion of SABV in preclinical CVD research is essential for addressing the needs of female patients.
• Overcoming barriers to inclusive model design is key to advancing equitable cardiovascular medicine.
• Implementing SABV will improve the translational validity of in vitro models and enhance treatment efficacy.