Pulmonary vascular disease in mice xenografted with human BM progenitors from patients with pulmonary arterial hypertension
Year: 2012
Type: article
Abstract: 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.
Source: Blood
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: Asthma Inflammation Research, G231556210, Schistosomiasis Associated Pulmonary Arterial Hypertension, Airway redox biochemistry as a deteriminant of asthma phenotype during adolescen*, Oxidation in Inflammation and Cardiovascular Disease, Nitric Oxide in Pulmonary Hypertension, Germline and Somatic Genetic Changes in Pulmonary Arterial Hypertension, Nitric Oxide in Pulmonary Hypertension, Clinical and Translational Science Collaborative of Cleveland, GENERAL CLINICAL RESEARCH CENTER, Case Comprehensive Cancer Center Support Grant
OpenAlex ID: W2060017024