Pregnancy-Induced Remodeling of Collagen Architecture and Content in the Mitral Valve
Pregnancy-Induced Remodeling of Collagen Architecture and Content in the Mitral Valve
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DOI：
10.1007/s10439-014-1077-6
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发表时间：
2014-10-01
影响因子：
3.8
通讯作者：
Wells, Sarah M.
中科院分区：
文献类型：
--
作者：
Pierlot, Caitlin M.;Lee, J. Michael;Wells, Sarah M.
由于胎儿生长的需要，怀孕会在母体循环中产生快速的、非病理性的容量超负荷。使用牛的人类妊娠模型，我们实验室以前的工作已经显示了妊娠引起的叶大小和二尖瓣机械结构的显著变化。本研究试图将这些变化与胶原小叶基质的结构变化联系起来。二尖瓣前叶取自非妊娠小母牛和妊娠母牛(妊娠期以胎长估计)。我们通过Verhoff-Van Gieson染色测量小叶及其解剖层厚度的变化，并通过天狼星红染色和偏光显微镜测量胶原卷曲(波长和百分比)的变化。用生化方法测定胶原浓度：羟脯氨酸测定法测定总胶原，胃酶-酸抽提法测定未交联胶原。小角光散射(SALS)评估了内部纤维结构的变化(以纤维排列程度和优先选择的纤维方向为特征)。妊娠使二尖瓣内胶原结构发生明显变化。纤维取向向径向旋转11.5度时，纤维对准程度降低了17%。胶原纤维卷曲显著消失，伴有53%的纤维增厚，总胶原浓度增加16%，这都表明新的胶原正在合成。在非妊娠和妊娠状态下，可提取的胶原浓度都很低，这表明新合成的胶原早期发生了交联。这项研究表明，二尖瓣在怀孕期间具有很强的适应性，随着需求的快速变化，二尖瓣的大小、胶原含量和结构都会发生显著变化。
Pregnancy produces rapid, non-pathological volume-overload in the maternal circulation due to the demands of the growing fetus. Using a bovine model for human pregnancy, previous work in our laboratory has shown remarkable pregnancy-induced changes in leaflet size and mechanics of the mitral valve. The present study sought to relate these changes to structural alterations in the collagenous leaflet matrix. Anterior mitral valve leaflets were harvested from non-pregnant heifers and pregnant cows (pregnancy stage estimated by fetal length). We measured changes in the thickness of the leaflet and its anatomic layers via Verhoeff-Van Gieson staining, and in collagen crimp (wavelength and percent collagen crimped) via picrosirius red staining and polarized microscopy. Collagen concentration was determined biochemically: hydroxyproline assay for total collagen and pepsin-acid extraction for uncrosslinked collagen. Small-angle light scattering (SALS) assessed changes in internal fiber architecture (characterized by degree of fiber alignment and preferred fiber direction). Pregnancy produced significant changes to collagen structure in the mitral valve. Fiber alignment decreased 17% with an 11.5A degrees rotation of fiber orientation toward the radial axis. Collagen fiber crimp was dramatically lost, accompanied by a 53% thickening of the fibrosa, and a 16% increase in total collagen concentration, both suggesting that new collagen is being synthesized. Extractable collagen concentration was low, both in the non-pregnant and pregnant state, suggesting early crosslinking of newly-synthesized collagen. This study has shown that the mitral valve is strongly adaptive during pregnancy, with significant changes in size, collagen content and architecture in response to rapidly changing demands.