Cardiac valve cells and their microenvironment—insights from in vitro studies

Abstract

During every heartbeat, cardiac valves open and close coordinately to control unidirectional flow of blood. In this dynamically challenging environment, resident valve cells actively maintain homeostasis, but the signalling between cells and their microenvironment is complex. When this homeostasis is disrupted and valve opening obstructed, haemodynamic profiles can be altered and lead to impaired cardiac function. Currently, late stages of cardiac valve diseases are treated surgically, as there are no known drug therapies to reverse or halt disease progression. Consequently investigators have sought to understand the molecular and cellular mechanisms of valvular diseases usi in vitro cell culture systems and biomaterials scaffolds that can mimic extracellular microenvironment. In this Review we describe how signals in the extra cellular matrix regulate valve cell function. We propose that the cellular context is a critical factor when studying the molecular basis of valvular diseases in vitro, and one should consider how the surrounding matrix might influence cell signalling and functional outcomes in the valve. Investigators need to build a systems level understanding of the complex signalling network involved in valve regulation, to facilitate drug target identification and promote in situ or ex vivo heart valve regeneration.

Histone Deacetylase 3 Coordinates Deacetylase-independent Epigenetic Silencing of Transforming Growth Factor-β1 (TGF-β1) to Orchestrate Second Heart Field Development

“…Hence, semilunar valve pathologies augment TGF-␤ bioavailability, which in turn promotes aberrant EndMT and transcriptional activation of smooth muscle and extracellular matrix genes within the myofibroblasts (24). TGF-␤ activation and aberrant extracellular matrix further promote the activation and differentiation of new valvular mesenchymal cells derived via EndMT (25). Consistent with these observations, our data dem- Isl1KO and control E14.5 semilunar valves.…”

“…Pathologic conditions promote activation and differentiation of valvular interstitial cells into myofibroblasts, smooth muscle-like fibroblasts that are observed in patients with semilunar valve disease (25). Myofibroblasts express smooth muscle-specific genes and secrete strikingly higher levels of TGF-␤, proteoglycans, and collagen that alter the composition of the extracellular matrix (19).…”

Dynamically tunable cell culture platforms for tissue engineering and mechanobiology

“…Biochemical cues also play a crucial role in directing cellular function and fate, and the relationship between their ‘static’ effect and cellular responses has been addressed by material-based and molecular biology approaches [15, 16]. However, we know that cellular microenvironments in vivo gradually change their physicochemical properties, as evidenced in cardiomyopathies and in cancer progression [17–19]. This dynamic nature, in turn, is closely related to tissue/organ development, regeneration, wound healing, and disease progression over time [20].…”

Integrated Bioinformatics Analysis Predicts the Key Genes Involved in Aortic Valve Calcification: From Hemodynamic Changes to Extracellular Remodeling

“…The overload of local hemodynamic stress has been regarded as a causative factor in the development and progression of CAVD (Balachandran et al 2011;Back et al 2013;Gould et al 2013;Wang et al 2014). GSE26953 datasets containing expression profiles of fHAVECs exposed to laminar/oscillatory shear stress were combined with the integrated expression profiles of human samples.…”