REVIEW article
Front. Cardiovasc. Med.
Sec. Cardiovascular Biologics and Regenerative Medicine
Volume 12 - 2025 | doi: 10.3389/fcvm.2025.1570271
Unveiling the Intricacies of Cardiac Valve Pathophysiology
Provisionally accepted
- 1Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Capital Region of Denmark, Denmark
- 2Department of Cardiothoracic and Vascular Surgery, Aarhus University Hospital, Aarhus, Denmark
- 3University Medical Center Hamburg-Eppendorf, Hamburg, Hamburg, Germany
- 4Department of Pathology, Aarhus University Hospital, Aarhus, Denmark
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Introduction Heart valves have long been regarded as uncomplicated, avascular, and passive structures. However, we hypothesise that their structure and function are complex. Therefore, we have reviewed the available literature to gain a profound understanding of their cellular composition and (patho)physiological behaviour. Methods A systematic search for articles related to the anatomy, histology, and physiology of heart valves was conducted using PubMed and Google Scholar, as well as a manual search of journals and websites. All publications were screened by title and abstract, and potentially eligible articles were reviewed in full text to assess their relevance. Results Cardiac valves comprise a complex, three-layered structure composed of an intricate network of cells. Valvular endothelial cells cover the atrial and ventricular sides of the valves. Valvular endothelial cells are morphologically and functionally distinct from vascular endothelial cells and play a crucial role in maintaining valve function. The three-valve layers, lamina fibrosa, spongiosa, and ventricularis, exhibit distinct biomechanical properties due to their varying extracellular matrix components and valvular interstitial cells. Valvular interstitial cells can be divided into four subtypes, each exhibiting specific cellular functions essential for normal valve physiology. However, pathological stimuli can cause aberrant activation of the valvular interstitial cells, leading to valve calcification and stenosis. Conclusion The intricate interplay of cellular components within cardiac valves is vital for maintaining normal valve function and structural integrity, but also contributes to valve pathology. A holistic understanding of heart valves, integrating cellular, molecular, and neural perspectives, is needed in the future.
Keywords: Valvular Heart Disease, Cardiac Valves, cardiac valve physiology, cardiac valve pathophysiology, Valve endothelial cells, Valve interstitial cells
Received: 03 Feb 2025; Accepted: 08 Jul 2025.
Copyright: © 2025 Jedrzejczyk, Hjertensgaard, Puelles and Hasenkam. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Johannes Jedrzejczyk, Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, 8000, Capital Region of Denmark, Denmark
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.