VEGF Inhibition and Renal Thrombotic Microangiopathy
| Autor: | Hans-Peter Gerber, J. Ashley Jefferson, Vera Eremina, Susan E. Quaggin, Napoleone Ferrara, Joseph Weisstuch, Charles E. Alpers, Catherine A. Richardson, Jeffrey B. Kopp, Peter H. Backx, Mark Haas, Jolanta Kowalewska, M. Golam Kabir, Howard S. Hochster, Laura Barisoni |
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| Rok vydání: | 2008 |
| Předmět: |
Male
Vascular Endothelial Growth Factor A Pathology medicine.medical_specialty Thrombotic microangiopathy Bevacizumab Kidney Glomerulus Angiogenesis Inhibitors Antibodies Monoclonal Humanized urologic and male genital diseases Renal Circulation Pathogenesis Mice chemistry.chemical_compound Neoplasms medicine Animals Humans RNA Messenger Aged Mice Knockout Kidney Podocytes Vascular disease business.industry Microcirculation Antibodies Monoclonal Thrombosis General Medicine Middle Aged medicine.disease Vascular endothelial growth factor Proteinuria Vascular endothelial growth factor A medicine.anatomical_structure chemistry Gene Targeting Immunology Onconephrology Female business Signal Transduction medicine.drug |
| Zdroj: | New England Journal of Medicine. 358:1129-1136 |
| ISSN: | 1533-4406 0028-4793 |
| Popis: | The glomerular microvasculature is particularly susceptible to injury in thrombotic microangiopathy, but the mechanisms by which this occurs are unclear. We report the cases of six patients who were treated with bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor (VEGF), in whom glomerular disease characteristic of thrombotic microangiopathy developed. To show that local reduction of VEGF within the kidney is sufficient to trigger the pathogenesis of thrombotic microangiopathy, we used conditional gene targeting to delete VEGF from renal podocytes in adult mice; this resulted in a profound thrombotic glomerular injury. These observations provide evidence that glomerular injury in patients who are treated with bevacizumab is probably due to direct targeting of VEGF by antiangiogenic therapy. |
| Databáze: | OpenAIRE |
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