Recipient-derived neoangiogenesis of arterioles and lymphatics in quilty lesions of cardiac allografts

Recipient-derived neoangiogenesis of arterioles and lymphatics in quilty lesions of cardiac allografts
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DOI:
10.1097/01.tp.0000287458.72440.75
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发表时间:
2007-11-27
期刊:
影响因子:
6.2
通讯作者:
Mengel, Michael
Mengel, Michael
中科院分区:
医学2区
文献类型:
--
作者:
Jonigk, Danny;Lehmann, Ulrich;Mengel, Michael

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背景心脏移植物中心外细胞对组织更新的贡献最近已被证实。复杂的内膜下浸润,称为Quilty病变,常在心脏移植物中观察到。Quilty病变的不同细胞成分的起源尚不清楚。分析了这些淋巴结浸润的不同成分与供体或受体来源的关系。激光辅助显微切割,随后短串联重复序列聚合酶链反应(PCR)为基础的“遗传指纹”。联合免疫荧光和荧光原位杂交的性染色体进行确认的情况下,性别不匹配的移植。通过实时定量逆转录PCR和荧光化学分析血管生成因子(FGF-2、PDGF-α、PDGF -α受体和VEGF-α)的表达。Quilty病变的炎性、非血管成分完全是受体源性的。血管来源多种多样。血管的不同隔室显示不同的受体衍生率(内皮细胞高达50%,平滑肌细胞高达15%)。淋巴管主要来源于受体。在血管生成分子中,与对照组和Quilty病变本身相比,VEGF-alpha在邻近心肌中的表达显著增加。Quilty病变的炎症区室是受体来源的,并显示血管和淋巴管的嵌合新血管生成。邻近心肌中产生的VEGF-alpha似乎刺激了嵌合新血管生成。
Background. The contribution of extracardiac cells to tissue turnover in heart allografts has recently been demonstrated. Complex subendocardial infiltrates, known as Quilty lesions, are frequently observed in cardiac allografts. The origin of the different cellular components of Quilty lesions is not known.Methods. Different constituents of these lymphonodular infiltrates were analyzed with regard to donor or recipient derivation. Laser-assisted microdissection with subsequent short tandem repeat polymerase chain reaction (PCR)based "genetic fingerprinting" was employed. Combined immunofluorescence and fluorescence in situ hybridization for sex chromosomes was performed for confirmation in cases of gender-mismatched transplantation. Expression of angiogenic factors (FGF-2, PDGF-alpha, PDGF - alpha- receptor, and VEGF-alpha) was analyzed by quantitative real-time reverse-transcription PCR and immunohistochemistry.Results. The inflammatory, nonvascular component of Quilty lesions was completely recipient- derived. Blood vessels were of mixed origin. Different compartments of blood vessels displayed different rates of recipient derivation (endothelium up to 50%, smooth muscle cells up to 15%). Lymphatic vessels were mainly recipient- derived. Of the angiogenic molecules, VEGF-alpha expression was significantly increased in the adjacent myocardium, compared to controls and the Quilty lesions themselves.Conclusions. The inflammatory compartment of Quilty lesions is of recipient origin and shows chimeric neoangiogenesis of blood and lymphatic vessels. VEGF-alpha produced in the adjacent myocardium appears to stimulate the chimeric neoangiogenesis.