Differential Changes in the Molecular Stability of Collagen from the Pulmonary and Aortic Valves During the Fetal-to-Neonatal Transition

Aldous, Ian G.; Lee, J. Michael; Wells, Sarah

doi:10.1007/s10439-010-0061-z

Cited by 13 publications

(6 citation statements)

References 37 publications

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“…Thus, a higher proportion of immature cross-links indicates a more rapid turnover rate of collagen (1,4). Treatment of our tissues with NaBH 4 significantly increased HIT t 1/2 for tissues from all pregnancy groups, indicating the presence of thermally labile, immature crosslinks.…”

Section: Discussionmentioning

confidence: 83%

Physiological remodeling of the mitral valve during pregnancy

Wells

Pierlot

Moeller

2012

American Journal of Physiology-Heart and Circulatory Physiology

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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.

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Section: Discussionmentioning

confidence: 83%

Physiological remodeling of the mitral valve during pregnancy

Wells

Pierlot

Moeller

2012

American Journal of Physiology-Heart and Circulatory Physiology

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“…Further, in a recent study that examined collagen hydrothermal stability of heart valve tissues, it was found that collagen in heart valves subjected to higher TVP had lower molecular stability and cross-linking (3). The molecular stability of the collagen in the AV also decreased compared to that of the PV from transition from fetal to neonatal when the TVP in the AV increases due to closure of the foramen ovale and ductus arteriosus (2). Aldous et al speculated from these findings that a relationship exists between the turnover rate of collagen and mechanical loading whereby there is a faster rate of damage accumulation and collagen turnover in the valves under higher TVP as a mechanism of resistance to biomechanical fatigue loading.…”

Section: Discussionmentioning

confidence: 99%

“…Further, at 90 mmHg the PV VIC undergoes a much larger deformation than the AV VIC, which can be reached in pulmonary hypertension or the Ross procedure. Hence, different levels of VIC deformation may lead to modification of ECM gene expression and architecture, as seen with age, disease, or repair (1, 2, 7, 19, 27). This information sets the foundation for a more detailed study on VIC tissue formation and remodeling as a function of hemodynamic loading and VIC-collagen micromechanical coupling.…”

Section: Discussionmentioning

confidence: 99%

Gene Expression and Collagen Fiber Micromechanical Interactions of the Semilunar Heart Valve Interstitial Cell

et al. 2012

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The semilunar (aortic and pulmonary) heart valves function under dramatically different hemodynamic environments, and have been shown to exhibit differences in mechanical properties, extracellular matrix (ECM) structure, and valve interstitial cell (VIC) biosynthetic activity. However, the relationship between VIC function and the unique micromechanical environment in each semilunar heart valve remains unclear. In the present study, we quantitatively compared porcine semilunar mRNA expression of primary ECM constituents, and layer- and valve-specific VIC-collagen mechanical interactions under increasing transvalvular pressure (TVP). Results indicated that the aortic valve (AV) had a higher fibrillar collagen mRNA expression level compared to the pulmonary valve (PV). We further noted that VICs exhibited larger deformations with increasing TVP in the collagen rich fibrosa layer, with substantially smaller changes in the spongiosa and ventricularis layers. While the VIC-collagen micro-mechanical coupling varied considerably between the semilunar valves, we observed that the VIC deformations in the fibrosa layer were similar at each valve's respective peak TVP. This result suggests that each semilunar heart valve's collagen fiber microstructure is organized to induce a consistent VIC deformation under its respective diastolic TVP. Collectively, our results are consistent with higher collagen biosynthetic demands for the AV compared to the PV, and that the valvular collagen microenvironment may play a significant role in regulating VIC function.

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“…Collagen fibers are one of the key players in the remodeling process, since these proteins are the main load-bearing component of many soft tissues. In particular, collagen fiber orientation and bundle formation through cross-linking [8,9] play a significant role in valvular tissue mechanics. As a consequence, the architecture of the collagen network has a major influence on the mechanical functionality of soft tissues, as well as on mechanically induced growth and remodeling processes.…”

Section: Introductionmentioning

confidence: 99%