Oscillatory fluid-induced mechanobiology in heart valves with parallels to the vasculature

Abstract

Forces generated by blood flow are known to contribute to cardiovascular development and remodeling. These hemodynamic forces induce molecular signals that are communicated from the endothelium to various cell types. The cardiovascular system consists of the heart and the vasculature, and together they deliver nutrients throughout the body. While heart valves and blood vessels experience different environmental forces and differ in morphology as well as cell types, they both can undergo pathological remodeling and become susceptible to calcification. In addition, while the plaque morphology is similar in valvular and vascular diseases, therapeutic targets available for the latter condition are not effective in the management of heart valve calcification. Therefore, research in valvular and vascular pathologies and treatments have largely remained independent. Nonetheless, understanding the similarities and differences in development, calcific/fibrous pathologies and healthy remodeling events between the valvular and vascular systems can help us better identify future treatments for both types of tissues, particularly for heart valve pathologies which have been understudied in comparison to arterial diseases.

Flow-Mediated Factors in the Pathogenesis of Hypoplastic Left Heart Syndrome

“…In terms of valvular development, it has been found that elongation and thinning of the valves can be independently regulated by fluid shear stresses, tensile stresses, and chronic cyclical stretches through mechanotransduction programs [ 37 , 38 , 39 ]. For instance, as reviewed elsewhere [ 40 , 41 ], it has been suggested that the side of the semilunar valve that faces the aorta (arterial side) experiences oscillatory shear stress (in response to reversing flows), while the side that faces the ventricle experiences laminar shear stress (in response to unidirectional flow). Recently, using a combination of in vivo and in vitro assays in fetal mice and chick embryos, it was demonstrated that, on the arterial side of the valve, mechanotransduction of low oscillatory shear stress through canonical Wnt signaling resulted in increased endocardial cell BMP signaling and cellular proliferation, leading to elongation and growth of the semilunar valve on the arterial side [ 37 ].…”

The Role of Cardiac Resynchronization Therapy for the Management of Functional Mitral Regurgitation

“…The loss of water, which is a major component of the extracellular matrix and contributes to tissue viscoelasticity, is likely responsible for reduced viscous relaxation. Therefore, these compositional alterations observed could have functional consequences on the valves resulting in stiffer, less extensible, and less viscous [ 26 , 27 , 28 , 29 , 30 , 31 , 32 ].…”

An Image-Based Computational Fluid Dynamics Study of Mitral Regurgitation in Presence of Prolapse

“…The major complications are atrial fibrillation or flutter, pulmonary arterial hypertension and heart failure [69]. Epidemiological studies estimated that MVR occurs in up to 10% of the worldwide population [41].…”