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• W1542949846 abstract "Hemolytic anemia associated pulmonary hypertension (PH) typically occurs in chronic diseases such as sickle cell anemia and thalassemia.  The contributions of chronic and intermittent hypoxia caused by the anemic state and the role of free hemoglobin (Hb) and iron have been debated in the literature.  The lifetime cycle of hypoxia in hemolytic anemia is an important contributor to the worsening of pulmonary vascular remodeling and increased pulmonary vascular disease.  However, the role of low, but continuous plasma Hb in combination with hypoxia has not been well studied.  As a result we initially designed a rat model to evaluate the specific effects of hypoxia and continuous levels of Hb on the progression of PH in a chronic setting.  In this model we observed that Hb delivered by an implanted refillable infusion pump had an additive effect on hypoxia driven PH, even at low Hb plasma concentrations (10-20 µM heme). Our observations were consistent with increased adventitia macrophage accumulation, oxidation and inflammation that consistently lead to more pronounced metrics of enhanced pulmonary vascular remodeling.   As a result we suggested this model would be useful to evaluate potential treatments for PH, specifically PH associated with hemolysis.  Effective treatments targeted directly at Hb induced PH associated with hemolytic anemia do not presently exist. Sickle cell anemia patients have undetectable levels of the Hb binding protein, haptoglobin (Hp).  Therefore we focused our efforts on the study of repeated dose Hp therapy to increase the circulatory Hp pool and maintain plasma Hb in a non-reactive intravascular compartmentalized Hb-Hp complex.  Here we review results from several studies utilizing this model, discuss the role of macrophages in PH disease progression, dissect the contributions of hypoxia and Hb in our model and suggest treatment strategies tested to reduce Hbs contribution of progressive complications of PH." @default.
• W1542949846 created "2016-06-24" @default.
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• W1542949846 date "2015-10-27" @default.
• W1542949846 modified "2023-09-23" @default.
• W1542949846 title "Hypoxic pulmonary hypertension and the role of extra-cellular hemoglobin in perivascular macrophage accumulation" @default.
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• W1542949846 doi "https://doi.org/10.14800/macrophage.884" @default.
• W1542949846 hasPublicationYear "2015" @default.
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