Beyond VICs: Shedding light on the overlooked VECs in calcific aortic valve disease

Abstract

Calcific aortic valve disease (CAVD) is prevalent in developed nations and has emerged as a pressing global public health concern due to population aging. The precise etiology of this disease remains uncertain, and recent research has primarily focused on examining the role of valvular interstitial cells (VICs) in the development of CAVD. The predominant treatment options currently available involve open surgery and minimally invasive interventional surgery, with no efficacious pharmacological treatment. This article seeks to provide a comprehensive understanding of valvular endothelial cells (VECs) from the aspects of valvular endothelium-derived nitric oxide (NO), valvular endothelial mechanotransduction, valvular endothelial injury, valvular endothelial-mesenchymal transition (EndMT), and valvular neovascularization, which have received less attention, and aims to establish their role and interaction with VICs in CAVD. The ultimate goal is to provide new perspectives for the investigation of non-invasive treatment options for this disease. The pathogenesis of Calcific Aortic Valve Disease (CAVD) is recognized as a complex process regulated by multiple factors and pathways. Key mechanisms include mechanical injury, valvular endothelial dysfunction, lipid deposition, and inflammatory responses, with valvular endothelial dysfunction acting as the initial trigger for other pathogenic mechanisms. As research continues, the role of valve endothelial cells (VECs) in CAVD and their interactions with valve interstitial cells (VICs) are garnering increasing attention. This article reviews the potential roles of VECs in the pathogenesis of CAVD, including aspects such as valvular endothelium-derived nitric oxide (NO), valvular endothelial mechanotransduction, valvular endothelial injury, valvular endothelial-mesenchymal transition (EndMT), and valvular neovascularization. The goal is to provide new insights for pharmacological research on CAVD. (Figure created with BioRender.com.) • CAVD has emerged as an urgent global public health issue, making the development of therapeutic drugs both critical and imperative. • The role of VECs in the pathogenesis of CAVD, as well as the increasing attention to the interconnections between VECs and VICs, is gaining prominence. • Valvular endothelium-derived NO, valvular endothelial mechanotransduction, valvular endothelial injury, valvular EndMT, and valvular neovascularization all play significant roles in the development and progression of CAVD. • The role of immune cells within the valvular tissue, as well as the interactions between these immune cells and both VECs and VICs, requires further detailed investigation. • Appropriate collaboration at the intersection of medicine and engineering can enhance the practical clinical applications of basic medical research.

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