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Published on: November 3, 2015
Sex in cardiovascular disease: Why this biological variable should be considered in in vitro models
Anna K McClain1, Peter P Monteleone2,3, Janet Zoldan1
1Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX 78751, USA.
Insights
Sex differences in cardiovascular disease (CVD) are significant, yet in vitro models often lack sex reporting. Incorporating sex as a biological variable (SABV) in preclinical research is crucial for equitable female patient treatment.
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.
Abstract:
Cardiovascular disease (CVD), the world's leading cause of death, exhibits notable epidemiological, clinical, and pathophysiological differences between sexes. Many such differences can be linked back to cardiovascular sexual dimorphism, yet sex-specific in vitro models are still not the norm. A lack of sex reporting and apparent male bias raises the question of whether in vitro CVD models faithfully recapitulate the biology of intended treatment recipients. To ensure equitable treatment for the overlooked female patient population, sex as a biological variable (SABV) inclusion must become commonplace in CVD preclinical research. Here, we discuss the role of sex in CVD and underlying cardiovascular (patho)physiology. We review shortcomings in current SABV practices, describe the relevance of sex, and highlight emerging strategies for SABV inclusion in three major in vitro model types: primary cell, stem cell, and three-dimensional models. Last, we identify key barriers to inclusive design and suggest techniques for overcoming them.
