New Insights on the Formation of the Mitral Valve Chordae Tendineae in Fetal Life.

IF 2.4 4区 医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS Journal of Cardiovascular Development and Disease Pub Date : 2024-11-15 DOI:10.3390/jcdd11110367
Meghan Martin, Kate Gillett, Parker Whittick, Sarah Melissa Wells
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Abstract

There is an increasing understanding that some mitral valve pathologies have developmental origins. The time course of valvulogenesis varies by animal model; in cattle, the branched chordae tendineae architecture becomes fully developed at full term. The mechanism by which chordae tendineae bifurcate during fetal development remains unknown. The current study presents a detailed description of bovine chordae tendineae formation and bifurcation during fetal development. Analysis of Movat Pentachrome-stained histological sections of the developing mitral valve apparatus was accompanied by micro-CT imaging. TEM imaging of chordae branches and common trunks allowed the measurement of collagen fibril diameter distributions. We observed a proteoglycan-rich "transition zone" at the junction between the fetal mitral valve anterior leaflet and chordae tendineae with "perforations" lined by MMP1/2 and Ki-67 expressing endothelial cells. This region also contained clusters of proliferating endothelial cells within the bulk of the tissue. We hypothesize this zone marks a region where chordae tendineae bifurcate during fetal development. In particular, perforations created by localized MMP activity serve as a site for the initiation of a "split" of a single chordae attachment into two. This is supported by TEM results that suggest a similar population of collagen fibrils runs from the branches into a common trunk. A clear understanding of normal mitral valvulogenesis and its signaling mechanisms will be crucial in developing therapeutics and/or tissue-engineered valve replacements.

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对胎儿期二尖瓣腱索形成的新认识
越来越多的人认识到,一些二尖瓣病变源于发育。瓣膜生成的时间过程因动物模型而异;在牛中,分叉的腱索结构在足月时发育完全。腱索在胎儿发育过程中分叉的机制仍不清楚。本研究详细描述了牛腱膜在胎儿发育过程中的形成和分叉。在对发育中的二尖瓣器进行Movat五色染色组织学切片分析的同时,还进行了显微CT成像。通过对脐带分支和共同主干的 TEM 成像,可以测量胶原纤维的直径分布。我们观察到,在胎儿二尖瓣前叶和腱索交界处有一个富含蛋白多糖的 "过渡区","过渡区 "内有由 MMP1/2 和 Ki-67 表达内皮细胞构成的 "穿孔"。该区域的大部分组织中还含有增殖的内皮细胞簇。我们推测,该区域标志着腱索在胎儿发育过程中分叉的区域。特别是,局部 MMP 活动造成的穿孔是单个腱索附着物 "分裂 "成两个的起始点。TEM结果表明,类似的胶原纤维群从分支进入共同的主干,这也支持了上述观点。清楚地了解正常的二尖瓣瓣膜生成及其信号机制对于开发治疗药物和/或组织工程瓣膜替代物至关重要。
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来源期刊
Journal of Cardiovascular Development and Disease
Journal of Cardiovascular Development and Disease CARDIAC & CARDIOVASCULAR SYSTEMS-
CiteScore
2.60
自引率
12.50%
发文量
381
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