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• W4313558359 abstract "Abstract Circulating cell‐free hemoglobin (CFH) is elevated in pulmonary arterial hypertension (PAH) and associated with poor outcomes but the mechanisms are unknown. We hypothesized that CFH is generated from the pulmonary circulation and inadequately cleared in PAH. Transpulmonary CFH (difference between wedge and pulmonary artery positions) and lung hemoglobin α were analyzed in patients with PAH and healthy controls. Haptoglobin genotype and plasma hemoglobin processing proteins were analyzed in patients with PAH, unaffected bone morphogenetic protein receptor type II mutation carriers (UMCs), and control subjects. Transpulmonary CFH was increased in patients with PAH ( p = 0.04) and correlated with pulmonary vascular resistanc (PVR) ( r s = 0.75, p = 0.02) and mean pulmonary arterial pressure (mPAP) ( r s = 0.78, p = 0.02). Pulmonary vascular hemoglobin α protein was increased in patients with PAH ( p = 0.006), especially in occluded vessels ( p = 0.04). Haptoglobin genotype did not differ between groups. Plasma haptoglobin was higher in UMCs compared with both control subjects ( p = 0.03) and patients with HPAH ( p < 0.0001); patients with IPAH had higher circulating haptoglobin levels than patients with HPAH ( p = 0.006). Notably, circulating CFH to haptoglobin ratio was elevated in patients with HPAH compared to control subjects ( p = 0.02) and UMCs ( p = 0.006). Moreover, in patients with PAH, CFH: haptoglobin correlated with PVR ( r s = 0.37, p = 0.0004) and mPAP ( r s = 0.25, p = 0.02). Broad alterations in other plasma hemoglobin processing proteins (hemopexin, heme oxygenase‐1, and sCD163) were observed. In conclusion, pulmonary vascular CFH is associated with increased PVR and mPAP in PAH and dysregulated CFH clearance may contribute to PAH pathology. Further study is needed to determine whether targeting CFH is a viable therapeutic for pulmonary vascular dysfunction in PAH." @default.
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• W4313558359 date "2023-01-01" @default.
• W4313558359 modified "2023-10-17" @default.
• W4313558359 title "Transpulmonary generation of cell‐free hemoglobin contributes to vascular dysfunction in pulmonary arterial hypertension via dysregulated clearance mechanisms" @default.
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• W4313558359 doi "https://doi.org/10.1002/pul2.12185" @default.
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