Pregnancy-Induced Remodeling of Heart Valves

Abstract

Although many cardiovascular tissues have been shown to remodel when exposed to chronic changes in hemodynamic stresses, little is known about the capacity of heart valves to adapt in a non-pathological state such as pregnancy. Pregnancy is a volume-overload state that triggers enlargement of the heart and valve orifices, thereby elevating valve leaflet stresses. The aim of this work was to (i) investigate pregnancy-induced alterations in valve leaflet biomechanics, (ii) perform structural studies defining the material basis for these changes, and (iii) link the observed structural and mechanical information using a structural constitutive model. Valve leaflets were harvested from non-pregnant heifers and pregnant cows. Gross leaflet structure was characterized by leaflet dimensions, and small-angle light scattering was used to assess changes in internal collagen fiber architecture. Tissue composition was determined using standard biochemical assays. Histological studies assessed architectural changes in cellular and matrix components. Leaflet mechanical properties were assessed using equibiaxial mechanical testing. Collagen thermal stability and crosslinking state was assessed using denaturation and hydrothermal isometric tension tests. We observed rapid and extensive heart valve remodeling in pregnancy, with alterations to leaflet geometry, fiber architecture, composition, biomechanics, and cellularity. All the valves expanded in pregnancy, via an increase in the production of collagen, with associated changes in tissue composition and structure of the collagen network (i.e. loss of crimp, crosslink maturation, and reduction in thermal stability). Our structural constitutive model suggests that there is an initial period of permanent set-like deformation where no remodeling occurs, followed by a remodeling phase that results in near-complete restoration of homeostatic tissue-level stresses and mechanical properties. Understanding the valvular adaptations to pregnancy may be fundamental both to developing interventions and treatments for valve disease and heart failure, as well as recognizing the implications of pregnancies on maternal long-term vascular risk.