Macrophage Transitions in Heart Valve Development and Myxomatous Valve Disease.
Macrophage Transitions in Heart Valve Development and Myxomatous Valve Disease.
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DOI：
10.1161/atvbaha.117.310667
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发表时间：
2018-03
期刊：
影响因子：
--
通讯作者：
Yutzey KE
中科院分区：
文献类型：
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作者：
Hulin A;Anstine LJ;Kim AJ;Potter SJ;DeFalco T;Lincoln J;Yutzey KE
造血细胞在心脏瓣膜中已有报道，但仍缺乏特征性。有趣的是，最近的研究显示，人类粘液瘤二尖瓣中有白细胞和巨噬细胞的渗透。然而，巨噬细胞在正常瓣膜和粘液瘤瓣膜病(MVD)中的时间和作用仍不清楚。目的是研究出生后心脏瓣膜成熟过程中白细胞的特征，并确定MVD中的巨噬细胞亚群。白细胞在出生后在心脏瓣膜中被检测到，并且在出生后瓣膜发育过程中其数量增加。流式细胞术和免疫染色分析表明，几乎所有的瓣膜白细胞都是髓系细胞，至少由2个定位不同的巨噬细胞亚群和树突状细胞组成。从出生后一周开始，CCR2+巨噬细胞的数量增加，与单核细胞的渗透群体一致，巨噬细胞定位于瓣叶的生物力学应力区。瓣膜白细胞维持CD45的表达，不产生大量的内皮细胞或间质细胞。在表现出粘液瘤特征的Axin2KO小鼠的主动脉和二尖瓣中观察到巨噬细胞谱系。黏液瘤小叶中可见CCR2+单核细胞的浸润和CD206表达的巨噬细胞的扩张，并可见修饰重链透明质酸的区域。在人的MVD中也观察到了类似的修饰透明质酸的共存和巨噬细胞数量的增加。我们的研究证实了心脏瓣膜中髓系细胞的异质性，并强调了巨噬细胞亚群的改变，特别是在MVD中，浸润性CCR2+单核细胞和CD206+巨噬细胞的存在增加。
Hematopoietic-derived cells have been reported in heart valves but remain poorly characterized. Interestingly, recent studies reveal infiltration of leukocytes and increased macrophages in human myxomatous mitral valves. Nevertheless, timing and contribution of macrophages in normal valves and myxomatous valve disease (MVD) are still unknown. The objective is to characterize leukocytes during postnatal heart valve maturation and identify macrophage subsets in MVD. Leukocytes are detected in heart valves after birth and their numbers increase during postnatal valve development. Flow cytometry and immunostaining analysis indicate that almost all valve leukocytes are myeloid cells, consisting of at least 2 differentially localized macrophage subsets and dendritic cells. Beginning a week after birth, increased numbers of CCR2+ macrophages are present, consistent with infiltrating populations of monocytes, and macrophages are localized in regions of biomechanical stress in the valve leaflets. Valve leukocytes maintain expression of CD45 and do not contribute to significant numbers of endothelial or interstitial cells. Macrophage lineages were examined in aortic and mitral valves of Axin2 KO mice that exhibit myxomatous features. Infiltrating CCR2+ monocytes and expansion of CD206-expressing macrophages are localized in regions where modified heavy chain hyaluronan is observed in myxomatous valve leaflets. Similar colocalization of modified hyaluronan and increased numbers of macrophages were observed in human MVD. Our study demonstrates the heterogeneity of myeloid cells in heart valves and highlights an alteration of macrophage subpopulations, notably an increased presence of infiltrating CCR2+ monocytes and CD206+ macrophages, in MVD.