Blockade of placental growth factor reduces vaso-occlusive complications in murine models of sickle cell disease
| Autor: | Shujun Yuan, Derek Sim, Perry Liu, Peter Bringmann, Martin Rosenbruch, Katalin Kauser, Keith Abe, Jian-Ming Gu |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Eotaxin Placental growth factor congenital hereditary and neonatal diseases and abnormalities Cancer Research Chemokine Spleen Anemia Sickle Cell 03 medical and health sciences chemistry.chemical_compound Mice hemic and lymphatic diseases Lactate dehydrogenase Genetics medicine Macrophage Animals Humans Vascular Diseases Molecular Biology biology business.industry Monocyte Membrane Proteins Proteins Cell Biology Hematology Antibodies Neutralizing Disease Models Animal 030104 developmental biology medicine.anatomical_structure chemistry Immunology biology.protein business Plasminogen activator |
| Zdroj: | Experimental hematology. 60 |
| ISSN: | 1873-2399 |
| Popis: | Vaso-occlusive crisis (VOC) is the most common and debilitating complication of sickle cell disease (SCD); recurrent episodes cause organ damage and contribute to early mortality. Plasma placental growth factor (PlGF) levels are elevated in SCD and can further increase under hypoxic conditions in SCD mice. Treatment with a PlGF-neutralizing antibody (anti-PlGF Ab) in SCD mice reduced levels of monocyte chemoattractant protein-3, eotaxin, macrophage colony-stimulating factor, and plasminogen activator inhibitor-1 significantly, and of macrophage-derived chemokine and macrophage inflammatory protein-3β moderately; this may contribute to inhibition of leukocyte recruitment, activation, and thrombosis. In subsequent experiments, anti-PlGF Ab treatment significantly reduced plasma lactate dehydrogenase levels, indicating possible reduction in cellular destruction and/or hemolysis. Histopathology studies revealed decreased incidence and severity of congestion in the lungs and spleen with repeated anti-PlGF Ab treatment. Furthermore, anti-PlGF Ab significantly reduced vaso-occlusion events under hypoxic conditions in a modified dorsal skinfold chamber model in SCD mice. Therefore, elevated PlGF levels may contribute to recruitment and activation of leukocytes. This can subsequently lead to increased pathology of affected organs in addition to mediating acute hypoxia/reoxygenation-triggered vaso-occlusion under SCD conditions. Thus, targeting PlGF may offer a therapeutic approach to reduce acute VOC and possibly alleviate long-term vascular complications in patients with SCD. |
| Databáze: | OpenAIRE |
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