Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX 78751, USA.
Ascension Texas Cardiovascular, Austin, TX 78705, USA.
Sci Adv. 2024 May 10;10(19):eadn3510. doi: 10.1126/sciadv.adn3510.
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.
心血管疾病（CVD）是全球主要的死亡原因，在性别方面表现出显著的流行病学、临床和病理生理学差异。许多此类差异可以追溯到心血管性别二态性，但仍未普遍采用针对特定性别的体外模型。缺乏性别报告和明显的男性偏见提出了一个问题，即体外 CVD 模型是否忠实地再现了预期治疗对象的生物学特性。为了确保被忽视的女性患者群体得到公平的治疗，必须将性别作为生物学变量（SABV）纳入 CVD 临床前研究。在这里，我们讨论了性别在 CVD 中的作用以及潜在的心血管（病理）生理学。我们回顾了当前 SABV 实践中的不足，描述了性别的相关性，并强调了在三种主要的体外模型类型中纳入 SABV 的新策略：原代细胞、干细胞和三维模型。最后，我们确定了包容性设计的关键障碍，并提出了克服这些障碍的技术。
