Role for circulating osteogenic precursor cells in aortic valvular disease.
Role for circulating osteogenic precursor cells in aortic valvular disease.
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DOI：
10.1161/atvbaha.111.234724
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发表时间：
2011-12
期刊：
影响因子：
--
通讯作者：
Pignolo RJ
中科院分区：
文献类型：
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作者：
Egan KP;Kim JH;Mohler ER 3rd;Pignolo RJ
大约13%的终末期主动脉瓣疾病患者的主动脉瓣含有异位骨化（HO）。最近，我们发现了一种新的循环成骨前体（COP）细胞，它们来源于骨髓，具有形成骨的能力。这些细胞通过共表达成骨标志物1型胶原或骨细胞素（OCN）和造血标志物CD 45来鉴定。我们检验了这些细胞可能导致心脏瓣膜狭窄的假设。通过流式细胞术对CD45+ OCN+ COP细胞的定量显示，它们占单核细胞的1.1%。通过免疫组织化学分析，克隆来源的COP细胞产生骨形态发生蛋白2和4。我们回顾了105例终末期主动脉瓣疾病，并在13个存档标本中证实了HO。使用免疫组化，我们确定COP细胞的CD45和1型胶原蛋白的共表达。COP细胞的存在与早期HO病变之间存在统计学显著相关性。COP细胞在来自相同个体的未受影响的瓣叶（无HO）区域中可忽略不计。这项研究提供了第一个证据，即血液中的成骨细胞归巢于血管损伤部位，并与心脏瓣膜中HO的形成有关。
Approximately 13 percent of aortic valves removed from patients with end-stage aortic valve disease contain heterotopic ossification (HO). Recently, we identified a novel population of circulating osteogenic precursor (COP) cells which are derived from bone marrow and have the capability to form bone. These cells are identified by co-expression of osteogenic marker types 1 collagen or osteoclacin (OCN) and the hematopoietic marker CD45. We tested the hypothesis that these cells may contribute to heart valve stenosis. Quantification of CD45+ OCN+ COP cells by flow cytometry showed that they represent up to 1.1 percent of mononuclear cells. Clonally-derived COP cells produce bone morphogenetic proteins 2 and 4 by immunohistochemical analysis. We reviewed 105 cases of end-stage aortic valvular disease and confirmed HO in 13 archived specimens. Using immunohistochemistry, we identified COP cells by co-expression of CD45 and type 1 collagen. There was a statistically significant association between the presence of COP cells and early HO lesions. COP cells were negligible in regions of unaffected valve leaflets (no HO) from the same individuals. This study provides the first evidence that osteogenic cells in the blood home to sites of vascular injury and are associated with HO formation in heart valves.