Figure 2: Sample sources for omics studies of CAVD.

Along with human studies, a number of well-defined animal models of calcific aortic valve disease (CAVD) exist with differing (dis)advantages.²¹⁷ Collection of valvular tissues or biofluids such as whole blood, plasma, or serum from human donors or model organisms can act as both direct inputs into multi-omics studies, or can be used for isolation and subsequent culture of valve-derived cells (e.g. valve interstitial cells [VICs] or valve endothelial cells [VECs]). Depending on experimental aims/context, these valve-derived cells can be maintained in standard 2D in vitro cultures, 3D organoid-style constructs, or in bioreactors that mimic aspects of native biomechanics (e.g. cyclic shear, stretch, or compression). Subsequently, DNA, RNA (mRNA or non-coding), protein, extracellular vesicles (EVs), or metabolites derived from cell culture supernatants or the cells themselves can be input into omics pipelines.