Bicuspid Aortic Valves With Different Spatial Orientations of the Leaflets Are Distinct Etiological Entities
Bicuspid Aortic Valves With Different Spatial Orientations of the Leaflets Are Distinct Etiological Entities
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DOI：
10.1016/j.jacc.2009.07.044
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发表时间：
2009-12-08
影响因子：
24
通讯作者：
Sans-Coma, Valentin
中科院分区：
文献类型：
--
作者：
Fernandez, Borja;Duran, Ana C.;Sans-Coma, Valentin
目的探讨右、非冠状叶融合二尖瓣(R-N)与左、右叶融合二尖瓣(R-L)是病因不同还是单一因素的产物。方法采用内皮型一氧化氮合酶基因敲除小鼠的成年心脏和胚胎心脏，以及R-N和R-L BAVs高发的近交系叙利亚仓鼠。采用组织化学、免疫组织化学和扫描电子显微镜等技术。结果R-N BAVs是由于心脏流出道(OT)心内膜垫发育缺陷，形成形态异常的右叶所致。左叶发育正常。R-L BAVs是隔区和顶区OT脊向外融合的结果，从而形成唯一的前叶。结论R-N和R-L是两种不同的病原学实体。R-N BAVs是在OT间隔之前发生的形态发生缺陷的产物，可能依赖于加剧的一氧化氮依赖的上皮向间充质转化。R-L BAVs是由OT近端的异常间隔引起的，可能是由神经脊细胞的扭曲行为引起的。R-N和R-L BAVs可能依赖于不同的基因型别，因此在今后的BAVs遗传学研究中应特别注意。应详细筛查R-N和R-L BAVs，以便更好地了解这些BAVs形态表型与其他心脏病的关系。(J Am Coll心脏ol 2009；54：2312-8)(C)美国心脏病学会基金会2009
Objectives The aim of this study was to decide whether bicuspid aortic valves (BAVs) with fused right and noncoronary leaflets (R-N) and BAVs with fused right and left leaflets (R-L) have different etiologies or are the product of a single diathesis.Background The BAV is the most common congenital cardiac malformation. The R-N and R-L BAVs are the most frequent BAV subtypes.Methods The study was carried out in adult and embryonic hearts of endothelium nitric oxide synthase knock-out mice and inbred Syrian hamsters with a high incidence of R-N and R-L BAVs, respectively. The techniques used were histochemistry, immunohistochemistry, and scanning electron microscopy.Results The R-N BAVs result from a defective development of the cardiac outflow tract (OT) endocardial cushions that generates a morphologically anomalous right leaflet. The left leaflet develops normally. The R-L BAVs are the outcome of an extrafusion of the septal and parietal OT ridges that thereby engenders a sole anterior leaflet. The noncoronary leaflet forms normally.Conclusions The R-N and R-L BAVs are different etiological entities. The R-N BAVs are the product of a morphogenetic defect that happens before the OT septation and that probably relies on an exacerbated nitric oxide-dependent epithelial-to-mesenchymal transformation. The R-L BAVs result from the anomalous septation of the proximal portion of the OT, likely caused by a distorted behavior of neural crest cells. Care should be taken in further work on BAV genetics because R-N and R-L BAVs might rely on different genotypes. Detailed screening for R-N and R-L BAVs should be performed for a better understanding of the relationships between these BAV morphologic phenotypes and other heart disease. (J Am Coll Cardiol 2009;54:2312-8) (C) 2009 by the American College of Cardiology Foundation