AUTHOR=Jedrzejczyk Johannes H. , Hjertensgaard Oline , Puelles Victor G. , Hasenkam J. Michael 

TITLE=Unveiling the intricacies of cardiac valve pathophysiology

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=Volume 12 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2025.1570271

DOI=10.3389/fcvm.2025.1570271

ISSN=2297-055X

ABSTRACT=IntroductionHeart 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.MethodsA 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.ResultsCardiac 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.ConclusionThe 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.