High levels of placenta growth factor in sickle cell disease promote pulmonary hypertension
| Autor: | Laurel Mendelsohn, Vijay K. Kalra, Tomoyasu Higashimoto, Janaka Wansapura, Nambirajan Sundaram, William C. Nichols, Punam Malik, Xunde Wang, Gregory J. Kato, Anitaben Tailor, Michael W. Pauciulo, William M. Gottliebson |
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| Rok vydání: | 2010 |
| Předmět: |
Adult
Hemolytic anemia medicine.medical_specialty Hypertension Pulmonary Immunology Enzyme-Linked Immunosorbent Assay Mice Transgenic Anemia Sickle Cell Pregnancy Proteins Biochemistry Cell Line Nitric oxide Mice chemistry.chemical_compound Red Cells Iron and Erythropoiesis Internal medicine medicine.artery medicine Animals Humans Placenta Growth Factor Mice Knockout Endothelin-1 business.industry Myocardium Respiratory disease Erythroid Hyperplasia Cell Biology Hematology medicine.disease Endothelin 1 Pulmonary hypertension Mice Inbred C57BL medicine.anatomical_structure Endocrinology chemistry Ventricle Pulmonary artery Hypertrophy Left Ventricular business |
| Zdroj: | Blood. 116:109-112 |
| ISSN: | 1528-0020 0006-4971 |
| Popis: | Pulmonary hypertension is associated with reduced nitric oxide bioavailability and early mortality in sickle cell disease (SCD). We previously demonstrated that placenta growth factor (PlGF), an angiogenic factor produced by erythroid cells, induces hypoxia-independent expression of the pulmonary vasoconstrictor endothelin-1 in pulmonary endothelial cells. Using a lentivirus vector, we simulated erythroid expression of PlGF in normal mice up to the levels seen in sickle mice. Consequently, endothelin-1 production increased, right ventricle pressures increased, and right ventricle hypertrophy and pulmonary changes occurred in the mice within 8 weeks. These findings were corroborated in 123 patients with SCD, in whom plasma PlGF levels were significantly associated with anemia, endothelin-1, and tricuspid regurgitant velocity; the latter is reflective of peak pulmonary artery pressure. These results illuminate a novel mechanistic pathway linking hemolysis and erythroid hyperplasia to increased PlGF, endothelin-1, and pulmonary hypertension in SCD, and suggest that strategies that block PlGF signaling may be therapeutically beneficial. This trial was registered at http://clinicaltrials.gov as #NCT00011648. |
| Databáze: | OpenAIRE |
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