In vitro models of aortic valve calcification: solidifying a system

Abstract

Calcific aortic valve disease (CAVD) affects 25% of people over 65, and the late-stage stenotic state can only be treated with total valve replacement, requiring 85,000 surgeries annually in the US alone [1]. As CAVD is an age-related disease, many of the affected patients are unable to undergo the open-chest surgery that is its only current cure. This challenge motivates the elucidation of the mechanisms involved in calcification, with the eventual goal of alternative preventative and therapeutic strategies. There is no sufficient animal model of CAVD, so we turn to potential in vitro models. In general, in vitro models have the advantages of shortened experiment time and better control over multiple variables compared to in vivo models. As with all models, the hypothesis being tested dictates the most important characteristics of the in vivo physiology to recapitulate. Here, we collate the relevant pieces of designing and evaluating aortic valve calcification so that investigators can more effectively draw significant conclusions from their results.

Microarray analyses to quantify advantages of 2D and 3D hydrogel culture systems in maintaining the native valvular interstitial cell phenotype

“…VICs are important regulators of valve ECM, but pathological VIC activation leads to excessive collagen deposition, a disorganized matrix, and valve fibrosis [6]. Mechanisms contributing to this disease state are still being elucidated, and there are no clinical treatments to slow or reverse valve fibrosis [4].…”

“…The VIC myofibroblast phenotype is characterized by the presence of prominent α-smooth muscle actin (αSMA) stress fibers and associated with increased proliferation, ECM remodeling, and cytokine secretion [2,6]. In vitro culture systems afford an opportunity to study this transition, especially as a function of VIC-matrix interactions and in the absence of the complex signaling milieu that occurs in vivo .…”

Robotic-assisted real-time MRI-guided TAVR: from system deployment to in vivo experiment in swine model

“…d, e Sheath was retracted to deploy the valve. f Valve deployed potentially utilizing existing in vitro or in vivo models with LDLR gene mutations, hypercholesterolemic diet induction, or traumatic provocation, should be considered [33][34][35][36]. Furthermore, the incorporation of common interventional adjuncts, such as guidewires or balloon catheters, will be essential; many institutions now utilize balloon valvuloplasty prior to TAVR in select cases of severe aortic stenosis [37,38].…”

Shape-Specific Nanoceria Mitigate Oxidative Stress-Induced Calcification in Primary Human Valvular Interstitial Cell Culture

“…19 However, these animal models may not fully share the pathobiology of human valve calcification. It was reported that porcine VICs did not form mineral deposits when treated with osteogenic media with TGF- β 1 20 and became contact-inhibited monolayers, which behave unstably during long-term cell culture.…”