Heart Valve Structure and Function in Development and Disease

Abstract

The mature heart valves are made up of highly organized extracellular matrix (ECM) and valve interstitial cells (VIC) surrounded by an endothelial cell layer. The ECM of the valves is stratified into elastin-, proteoglycan- and collagen-rich layers that confer distinct biomechanical properties to the leaflets and supporting structures. Signaling pathways have critical functions in primary valvulogenesis as well as maintenance of valve structure and function over time. Animal models provide powerful tools to study valve development and disease processes. Valve disease is a significant public health problem and increasing evidence implicates aberrant developmental mechanisms underlying pathogenesis. Further studies are necessary to determine regulatory pathway interactions underlying pathogenesis in order to generate new avenues for novel therapeutics.

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

“…Remodeling of valvular interstitial cells and extracellular matrix, mainly collagens, proteoglycans, and elastin, is essential for maturation of the semilunar valves (61). Hdac3…”

Molecular Mechanisms of Heart Valve Development and Disease

“…Wnt/β-catenin signaling also is active during endocardial cushion maturation, but the specific role for this pathway in valve lineage differentiation is yet to be determined [10]. Valve development continues with the remodeling of the endocardial cushions into thin elongated leaflets composed of stratified ECM, which occurs soon after birth in mice and humans [2]. The ECM layers consist of the collagen-rich fibrosa, proteoglycan-rich spongiosa, and elastin-rich atrialis/ ventricularis [2].…”

“…Valve development continues with the remodeling of the endocardial cushions into thin elongated leaflets composed of stratified ECM, which occurs soon after birth in mice and humans [2]. The ECM layers consist of the collagen-rich fibrosa, proteoglycan-rich spongiosa, and elastin-rich atrialis/ ventricularis [2]. These layers are oriented in the semilunar and AV valves with the elastin layer adjacent to blood flow.…”

“…In healthy valves, the ECM is compartmentalized into layers composed of collagens, proteoglycans, and elastin, which are maintained by the VICs for proper valve function throughout life (Reviewed in [2]). In diseased valves, the leaflets are thickened as a result of ECM dysregulation and VIC activation.…”

Comparison of Mesenchymal Stem Cell Source Differentiation Toward Human Pediatric Aortic Valve Interstitial Cells within 3D Engineered Matrices

“…4,77 The aortic valve leaflet is known to exhibit a complex tri-layer striation with ECM components, mainly GAGs, collagen, and elastin. 77 We thus quantitatively evaluated and compared the secretion and remodeling of these ECM components. We observed that all these three cell types were able to dynamically produce and remodel their own matrix within the hydrogels.…”