Comparison of human and porcine aortic valve endothelial and interstitial cells

Abstract

Calcific aortic valve disease (CAVD) is one of the most common heart valve pathologies and a major cause of morbidity and mortality in the elderly population. The disease is characterized by the gradual accumulation of calcium deposits in the cusps, leading to stiffening and restricted movement of the valve. This can lead to aortic valve stenosis (AVS), a condition characterized by the narrowing of the valve orifice and diminished blood flow from the heart. Currently, there are no medical treatment strategies that can stop or delay the development of CAVD. The only treatment option is to replace the aortic valve through surgical aortic valve replacement (SAVR) or transcatheter aortic valve implantation (TAVI). During CAVD, pathological changes occur in the biology of the aortic valve and the predominant cell types, valvular interstitial cells (VICs) and endothelial cells (VECs). The geno- and phenotypic changes of resident cells play a critical role in the process of valve calcification. However, the extent of their contribution and their specific functions in this process remain poorly understood, despite extensive research in recent years. Understanding the mechanisms of cellular and molecular involvement in the pathobiology of this disease is a prerequisite for identifying potential pharmacological and non-surgical/non-interventional treatment strategies. <br> In this study, an optimized cell isolation method was implemented to directly isolate aortic valve cells for <em>in vitro</em> studies and to initiate the standardization of this method, which may improve the comparability of results between different laboratories. Human aortic valve tissue, which was explanted for CAVD or aortic insufficiency (AI) was used to isolate VECs and VICs. Because not all researchers may have access to human material and due to the increasing interest in a porcine animal model of CAVD, readily available porcine VECs and VICs were also isolated. Moreover, these cells were characterized and a comprehensive comparison of human and porcine VECs and VICs was performed. The cells were analyzed in <em>in vitro</em> calcification and endothelial-to-mesenchymal transition (EndMT) models, established methods to study the involvement of aortic valve cell differentiation during the progression of CAVD. The results support the hypothesis that porcine cells resemble human cells and that porcine cells may serve as an alternative cellular model system.