Physiological remodeling of the mitral valve during pregnancy

Abstract

There is growing evidence that heart valves are not passive structures but can remodel with left ventricular dysfunction. To determine if these tissues remodel under nonpathological conditions, we examined the mirtal valve anterior leaflet during the volume loading and cardiac expansion of pregnancy using a bovine model. We measured leaflet dimensions, chordal attachments, and biaxial mechanical properties of leaflets collected from never-pregnant heifers and pregnant cows (pregnancy duration estimated from fetal length). Hydrothermal isometric tension (HIT) tests were performed to assess the denaturation temperature (T(d)) associated with collagen molecular stability and the load decay half-time (t(1//2)) associated with intermolecular cross-linking. Histological changes were examined using Verhoeff-van Gieson and picrosirius red staining with polarized light. We observed striking changes to the structure and material properties of the mitral anterior leaflet during pregnancy. Leaflet area was increased 33%, with a surprising increase (nearly 25%) in chordae tendinae attachments. There was a biphasic change in leaflet extensibility: it rapidly decreased by 30% and then reversed to prepregnant values by late pregnancy. The 2°C decrease in T(d) in pregnancy was indicative of collagen remodeling, whereas the 70% increase in HIT t(1/2) indicated an increase in collagen cross-linking. Finally, histological results suggested transient increases in leaflet thickness and transient decreases in collagen crimp. This remodeling may compensate for the increased loading conditions associated with pregnancy by normalizing leaflet stress and maintaining coaptation. Understanding the mechanisms of mitral valve physiological remodeling in pregnancy could contribute to alternative treatments of pathological remodeling associated with left ventricular dysfunction.

Mitral valve leaflet remodelling during pregnancy: insights into cell-mediated recovery of tissue homeostasis

“…In this study, we used extant biaxial mechanical data from a previous study, for which experimental testing methods have been described previously [12]. Briefly, fresh MV anterior leaflets from five never-pregnant heifers (NP) and 10 pregnant cows (P) at a variety of gestational time points were excised, laid flat, and their in-plane dimensions (circumferential length ' cir and radial length ' rad ) were measured, using a ruler of 1 mm resolution.…”

“…Previous animal studies have uncovered significant mechanical, structural and compositional changes in all four heart valves during pregnancy (table 1) [5,12 -14]. The mechanical behaviour of the MV anterior leaflet has been shown to undergo a biphasic change during pregnancy, with the apparent stiffness of the leaflet increasing significantly in early pregnancy (EP) but returning to normal by late pregnancy (LP) [12]. In contrast, a more recent investigation into structural changes of MV collagen during pregnancy uncovered no biphasic changes, but instead found only monotonic changes in mass fraction, preferred fibre direction, degree of fibre alignment and crimp period [13].…”

Pregnancy-induced remodeling of heart valves

“…Many investigations of valve adaptation have focused on physiological development (8,20,(51)(52)(53) or pathological conditions such as left ventricular (LV) dysfunction (10), mitral valve regurgitation (58), myxomatous degeneration (19), or heart failure (17). Recent studies from our laboratory, however, have demonstrated the capacity of maternal heart valve leaflets to remodel under the altered hemodynamics of pregnancy, a nonpathological condition (38,39,60). Pregnancy is accompanied by an increase in blood volume and cardiac output of ϳ50%, as the maternal circulation accommodates the developing fetoplacental unit.…”

“…These changes in geometry then elevate stresses on closed valve leaflets per the Law of Laplace (26). Our studies of the aortic and mitral valves have thus far shown dramatic increases in leaflet size of both valves accompanied by alterations in fiber architecture and composition, a decrease in thermal stability of collagen, a reversible shift in leaflet extensibility, and valve-specific alterations in resistance to creep (38,39,60). Together, these results provide strong evidence of both collagen turnover during pregnancy and unexpected maturation of native leaflet collagen, a complex restructuring of the collagen matrix under the altered cardiovascular loading and hormonal shifts of pregnancy.…”

“…Pregnancy is accompanied by an increase in blood volume and cardiac output of ϳ50%, as the maternal circulation accommodates the developing fetoplacental unit. This volume overload produces cardiac enlargement (21,45,60) with expansion of valve orifices (areas increasing from 12-53% in humans; see Refs. 9 and 43).…”