Hemoglobin-induced lung vascular oxidation, inflammation, and remodeling contribute to the progression of hypoxic pulmonary hypertension and is attenuated in rats with repeated-dose haptoglobin administration
| Autor: | Eva Nozik-Grayck, Zoe Loomis, Kurt R. Stenmark, Rachelle Nuss, Kathryn L. Hassell, David Irwin, Paul W. Buehler, Paul Eigenberger, Joanne Maltzahn, Christina Lisk, Jin Hyen Baek |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Lung Diseases
Male Hypertension Pulmonary Iron Inflammation Vascular Remodeling Pharmacology Biochemistry Article Cell Line Muscle hypertrophy Rats Sprague-Dawley Hemoglobins Physiology (medical) Macrophages Alveolar medicine Animals Vascular Diseases Hypoxia Lung Haptoglobins Hypertrophy Right Ventricular biology business.industry Haptoglobin Acute kidney injury Pneumonia Hypoxia (medical) Intercellular Adhesion Molecule-1 medicine.disease Pulmonary hypertension Rats Disease Models Animal medicine.anatomical_structure Immunology Disease Progression biology.protein Vascular Resistance Hemoglobin medicine.symptom business Oxidation-Reduction |
| Zdroj: | Free Radical Biology and Medicine. 82:50-62 |
| ISSN: | 0891-5849 |
| Popis: | Haptoglobin (Hp) is an approved treatment in Japan for trauma, burns, and massive transfusion-related hemolysis. Additional case reports suggest uses in other acute hemolytic events that lead to acute kidney injury. However, Hp's protective effects on the pulmonary vasculature have not been evaluated within the context of mitigating the consequences of chronic hemoglobin (Hb) exposure in the progression of pulmonary hypertension (PH) secondary to hemolytic diseases. This study was performed to assess the utility of chronic Hp therapy in a preclinical model of Hb and hypoxia-mediated PH. Rats were simultaneously exposed to chronic Hb infusion (35 mg per day) and hypobaric hypoxia for 5 weeks in the presence or absence of Hp treatment (90 mg/kg twice a week). Hp inhibited the Hb plus hypoxia-mediated nonheme iron accumulation in lung and heart tissue, pulmonary vascular inflammation and resistance, and right-ventricular hypertrophy, which suggests a positive impact on impeding the progression of PH. In addition, Hp therapy was associated with a reduction in critical mediators of PH, including lung adventitial macrophage population and endothelial ICAM-1 expression. By preventing Hb-mediated pathology, Hp infusions: (1) demonstrate a critical role for Hb in vascular remodeling associated with hypoxia and (2) suggest a novel therapy for chronic hemolysis-associated PH. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect