The role of the extracellular matrix in the development of heart valve disease: Underestimation or undercomprehension?

The function of metalloproteinases of the extracellular matrix and their inhibitors has emerged with a crucial role in valve diseases. Both the expression of matrix metalloproteinases and their inhibitors are susceptible to modification in patients with severe mitral insufficiency. This process is due to substantial changes in the collagen structure during mechanical stress on the mitral valve leaflets. Several studies have measured the level of deformation of the mitral leaflets with the use of the finite element analysis method by establishing the stiffness of the cellular and extracellular elements of the mitral valve leaflets. Evidence suggested the possible underestimation of the stiffness of the leaflets. This implies greater stress on the components of the extracellular matrix in the circumferential and radial strains that involve the mitral leaflets during chronic regurgitation. The remodeling process during mechanical stress phenomena involves both the cellular compartment and the extracellular matrix and can be adaptive or maladaptive as showed in patients who receive a pulmonary autograft to replace the diseased aortic valve. However, adaptive remodeling can be driven using resorbable polymers that interfere with the extracellular matrix. Further investigation is required for the understanding of the mechanisms that determine the structural changes of the extracellular matrix and to prevent them.