Pulmonary vascular disease in mice xenografted with human BM progenitors from patients with pulmonary arterial hypertension
Pulmonary vascular disease in mice xenografted with human BM progenitors from patients with pulmonary arterial hypertension
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DOI：
10.1182/blood-2012-03-419275
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发表时间：
2012-08-09
期刊：
影响因子：
20.3
通讯作者：
Erzurum, Serpil C.
中科院分区：
文献类型：
--
作者：
Asosingh, Kewal;Farha, Samar;Erzurum, Serpil C.
释放到循环中的造血骨髓祖细胞能够通过内皮活化和损伤促进血管重塑。内皮损伤是肺动脉高压（PAH）发展的核心，PAH是肺循环的增殖性血管病变，但血管损伤的起源尚不清楚。在本研究中，移植来自PAH患者而非健康对照的BM衍生的CD 133（+）祖细胞的小鼠，由于PAH的特征而表现出发病和/或死亡：原位血栓和内皮损伤、血管增生性重塑和右心室肥大和衰竭。来自遗传性和/或特发性PAH患者的髓系祖细胞在异种移植小鼠中均产生疾病。造血转录因子和集落形成的分析揭示了潜在的异常的祖细胞向骨髓-红系分化倾斜。本研究的结果表明造血干细胞异常在血管损伤、右心室肥大和PAH相关发病率中具有因果作用。（血。2012;120（6）：1218-1227）
Hematopoietic myeloid progenitors released into the circulation are able to promote vascular remodeling through endothelium activation and injury. Endothelial injury is central to the development of pulmonary arterial hypertension (PAH), a proliferative vasculopathy of the pulmonary circulation, but the origin of vascular injury is unknown. In the present study, mice transplanted with BM-derived CD133(+) progenitor cells from patients with PAH, but not from healthy controls, exhibited morbidity and/or death due to features of PAH: in situ thrombi and endothelial injury, angioproliferative remodeling, and right ventricular hypertrophy and failure. Myeloid progenitors from patients with heritable and/or idiopathic PAH all produced disease in xenografted mice. Analyses of hematopoietic transcription factors and colony formation revealed underlying abnormalities of progenitors that skewed differentiation toward the myeloid-erythroid lineage. The results of the present study suggest a causal role for hematopoietic stem cell abnormalities in vascular injury, right ventricular hypertrophy, and morbidity associated with PAH. (Blood. 2012;120(6):1218-1227)