Cellular Mechanisms in Mitral Valve Disease

Abstract

The mitral valve is a living structure comprised of specific structural components which contain a heterogeneous population of cells. The cells include an amalgam of interstitial cells within the valve and a continuous covering of endothelial cells, each of which play a role in responding to the mechanical forces that the valve experiences, to maintain the function and durability of the valve. Attention on the characteristics and function of valve cells has focused mainly on those in the aortic valve, with relatively few studies addressing the role of these cells in the physiological and pathophysiological function of the mitral valve. This article reviews what is known about the function of cells within the mitral valve and how the changes in the physical and chemical environments can affect their function in the different types of mitral valve disease. Investigating the contribution of the cellular components of the mitral valve to valve function in health and disease will aid the understanding of how the durability and function of the valve are regulated, and possibly highlight molecular and pharmacological targets for the development of novel treatments for mitral valve disease.

Epidemiology and Pathophysiology of Mitral Valve Prolapse

“…3, 66 Activated myofibroblasts are responsible for increased concentrations of various proteolytic enzymes, including matrix metalloproteinases, which degrade collagen and elastin at a rate exceeding the rate of production seen in quiescent VICs. 67 In addition, cells staining for the pan-hematopoietic marker CD45+ are also be found in myxomatous valve tissue, 66 and may represent fibrocytes capable of differentiating into myofibroblasts that can both secrete matrix and degrade collagen and elastin.…”

“…Several genes have been shown to play pivotal roles in the formation of the heart valves: calcineurin , with the signaling and downstream activation of a family of transcription factorsnamed Nuclear factor of activated T-cells (NFAT); the absence of NFAT activation leads to fatal defects in cardiac valve formation; 73 Wnt/beta-catenin signaling, which determines the fate of the endocardial cells during valve development; 74 fibroblast growth factor (FGF)-4 , the homeobox gene Sox4 , and the downstream modulator of TGF-β superfamily signaling SMAD6 , 67, 75 the disruption of which leads to abnormally thickened, gelatinous valves. Defects in one or more of these genes and their signaling cascades may also conceivably lead to myxomatous change and mechanically weakened valves in adult life.…”

Emerging pathogenic mechanisms in human myxomatous mitral valve: lessons from past and novel data

“…Although MMV disease is the most frequent cause of nonischemic mitral regurgitation in industrialized countries, effective pharmacological treatment preventing or reducing its progression is currently not available. This might be related to the sparsity of dedicated studies that address the cellular alterations and molecular mechanisms regulating the different phases of the myxomatous degeneration development and worsening [6] Available data in the literature suggest that cells that reside within the valve, collectively called valvular interstitial cells (VICs), might be the key actors. VICs include cells displaying phenotypic features of fibroblasts, myofibroblasts, smooth muscle cells, and progenitors and exchange information with the endothelial layer covering the valvular tissue.…”

Stabilized Collagen and Elastin-Based Scaffolds for Mitral Valve Tissue Engineering

“…This might be significant for MV durability, as the in vivo fragmentation of collagen organization in fibrosa and elastic fibers in the atrialis leads to MV prolapse and insufficiency. 45 The weak and enlarged ''floppy'' leaflets are associated with chordal elongation, thinning, and/or rupture. Indeed, PGG prevents the fragmentation of collagen and elastin fibers and, consequently, the alterations of the mechanical properties (Fig.…”