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Calcific aortic valve disease (CAVD) affects over 25% of individuals over the age of 65, making it the most prevalent valvular disease. Advanced age is the primary risk factor for CAVD, but biological sex follows close behind, wherein males are twice as likely as females to develop CAVD (Alushi et al. Front Pharmacol 11:685, 2020). This sex difference in disease prevalence has long been recognized, but ongoing research continues to reveal myriad cellular-scale sex differences that underlie the pathogenesis of this disease. Some of these cellular-scale sex differences are present at birth, while others are acquired, often in response to sex hormone signaling. Ultimately, sex differences in valvular function manifest in CAVD, taking a different form in men vs. women: in men, valvular stiffening is associated with calcification, while in women it is primarily due to fibrosis (Simard et al. Circ Res 120:681–91, 2017). This chapter discusses the complex interplay between different types of valvular cells, the extracellular matrix, aging processes, and sex differences in the development of CAVD. These characteristics are also discussed in the context of constructing valvular biomaterials, as engineered tissue models provide a promising avenue for furthering our understanding of disease pathogenesis, sexual dimorphisms, and potential therapeutic targets to mitigate CAVD severity.

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Sex-Based Insights into Aortic Valve Disease and Scaffold Design

  • 章节

  • 发表日期：

    2026年

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  • Joshita Suresh,
  • Nafeesah Ibrahim,
  • Kristyn S. Masters

摘要

Calcific aortic valve disease (CAVD) affects over 25% of individuals over the age of 65, making it the most prevalent valvular disease. Advanced age is the primary risk factor for CAVD, but biological sex follows close behind, wherein males are twice as likely as females to develop CAVD (Alushi et al. Front Pharmacol 11:685, 2020). This sex difference in disease prevalence has long been recognized, but ongoing research continues to reveal myriad cellular-scale sex differences that underlie the pathogenesis of this disease. Some of these cellular-scale sex differences are present at birth, while others are acquired, often in response to sex hormone signaling. Ultimately, sex differences in valvular function manifest in CAVD, taking a different form in men vs. women: in men, valvular stiffening is associated with calcification, while in women it is primarily due to fibrosis (Simard et al. Circ Res 120:681–91, 2017). This chapter discusses the complex interplay between different types of valvular cells, the extracellular matrix, aging processes, and sex differences in the development of CAVD. These characteristics are also discussed in the context of constructing valvular biomaterials, as engineered tissue models provide a promising avenue for furthering our understanding of disease pathogenesis, sexual dimorphisms, and potential therapeutic targets to mitigate CAVD severity.