The mechanobiology of mitral valve function, degeneration, and repair

Abstract

In degenerative valve disease, the highly organized mitral valve leaflet matrix stratification is progressively destroyed and replaced with proteoglycan rich, mechanically inadequate tissue. This is driven by the actions of originally quiescent valve interstitial cells that become active contractile and migratory myofibroblasts. While treatment for myxomatous mitral valve disease in humans ranges from repair to total replacement, therapies in dogs focus on treating the consequences of the resulting mitral regurgitation. The fundamental gap in our understanding is how the resident valve cells respond to altered mechanical signals to drive tissue remodeling. Despite the pathological similarities and high clinical occurrence, surprisingly little mechanistic insight has been gleaned from the dog. This review presents what is known about mitral valve mechanobiology from clinical, in vivo, and in vitro data. There are a number of experimental strategies already available to pursue this significant opportunity, but success requires the collaboration between veterinary clinicians, scientists, and engineers.

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

“…The MV composition and structure, and its pathology, needs to be taken into consideration to develop a robust and functional tissue-engineered MV, resistant to degenerative factors. 3,40 The MV accomplishes a complex and stressful mechanical effort during the cardiac cycle 10,41 that demands the integrity of all the components of the MV apparatus: the anterior leaflet, positioned in a fibrous continuity (fibrous annulus) with the noncoronary leaflets of the aortic valve, and a posterior leaflet, attached through the muscular part of the annulus to the left ventricle; the flexible chordae tendinae, which reinforce the leading edges of both leaflets, and continue with papillary muscles; the papillary muscles that function as shock absorbers and compensate for the geometric changes of the left ventricular wall. This mechanism maintains constant the papillary-annulus distance during the cardiac cycle, while the distance between the papillary muscles and the apex varies significantly, due to the presence of chordae, the principal force transmission during left ventricular ejection.…”

“…[3][4][5] The mechanical stress is transmitted to VICs through their interactions with the extracellular matrix (ECM) (mechanotransduction). [6][7][8][9][10] The MV surface is covered with endothelial cells, which interact with VICs to maintain the integrity of valves and also regulate the leaflets' mechanical properties. 11 MV insufficiency leading to regurgitation affects >2% of the population and, most frequently, is caused by mitral valve prolapse (MVP).…”

Myxomatous valve degeneration

“…[20] Structure and function av valves are a unique tissue exposed to a complex mechanical environment that consists of two leaflets: the anterior (septal) and the posterior (parietal) with unique morphological characteristics. [22] The cellular component of the cardiac valves consists mainly of endothelial, interstitial and smooth muscle cells, of which the interstitial cells play a critical role in maintaining valvular competence and counteracting biomechanical problems. [23] This means they are an active and dynamic component of the valves, which allows them to remodel in response to stressors.…”

“…The chordae tendineae modulate stress transmission to the leaflets, which is evidenced by the heterogeneity of mechanical properties and microstructure of the insertion of the strings in the leaflet. [22] The functions of the mitral and tricuspid apparatus are to keep the valve open during diastole to allow proper filling of the ventricles and to close smoothly without allowing blood backflow during ventricular systole. [27] In order for this heart valve to work properly, many related structures must also function correctly, such as the av ring, the av leaflets, the chordae that hold them, the papillary muscles and the myocardium.…”

Contractile Properties of the Right Atrial Myofilaments in Patients with Myxomatous Mitral Valve Degeneration

“…The tri-layered structure of the valve as well as the organization of the matrix structure is destroyed by accumulation of mechanically inadequate glycosaminoglycans which are increased in this tissue [3]. Further collagen fibrils change their organization structure and loose mechanical stability and flexibility [4]. This finding is not uncommon and also often found in a localized form [5].…”