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.

Figure 1

Representative stress-strain curve of a soft tissue under uniaxial tension with values relevant to the mitral valve, with uncrimping and aligning of collagen fibers as stress increases.

Figure 2

Atrial view of the closed mitral valve, showing gradations of tissue stiffness. Valve has highest stiffness (least deformation under applied load) at the annulus and lowest stiffness at the free edge, where the valve tissue experiences largest deformations.

Figure 3

Mechanical environment of the mitral valve under normal and pathological conditions. The mitral valve experiences a complex mechanical loading profile that changes dramatically during disease conditions. Red: general blood flow patterns, green: regions of elevated tissue stress, blue: degree of chordal tension. The combination of these forces exacerbates structural remodeling, but it is not yet known whether the underlying mechanisms for each component are similar.