Red blood cell exosome hemoglobin content increases after cardiopulmonary bypass and mediates acute kidney injury in an animal model
| Autor: | Joo-Yeun Oh, Michael Mrug, Clifton T. Lewis, Joshua S. Richman, James E. Davies, Pamela C. Powell, Juan Xavier Masjoan Juncos, Inmaculada Aban, Wayne E. Bradley, Betty Pat, Louis J. Dell’Italia, David Middleton, James F. Collawn, Orlando M. Gutiérrez, Rakesh P. Patel, Efstathia Andrikopoulou |
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| Rok vydání: | 2020 |
| Předmět: |
Pulmonary and Respiratory Medicine
medicine.medical_specialty Erythrocytes 030204 cardiovascular system & hematology Exosomes law.invention Rats Sprague-Dawley 03 medical and health sciences Hemoglobins 0302 clinical medicine Lipocalin-2 law Internal medicine Cardiopulmonary bypass Medicine Animals Kidney Cardiopulmonary Bypass biology Haptoglobins urogenital system business.industry Microvesicle Haptoglobin Acute kidney injury Hemopexin Acute Kidney Injury medicine.disease Rats Red blood cell Disease Models Animal medicine.anatomical_structure Endocrinology 030228 respiratory system biology.protein Surgery Hemoglobin Cardiology and Cardiovascular Medicine business Biomarkers |
| Zdroj: | The Journal of thoracic and cardiovascular surgery. 164(6) |
| ISSN: | 1097-685X |
| Popis: | Objective Hemolysis, characterized by formation of free hemoglobin (Hb), occurs in patients undergoing cardiopulmonary bypass (CPB). However, there is no study of the dynamic changes in red blood cell (RBC)-derived exosomes (Exos) released during CPB, nor whether these particles mediate acute kidney injury (AKI). Methods This study is a comprehensive time–course analysis, at baseline, 30 minutes, to 24 hours post-crossclamp release (XCR) to determine (1) Exos Hb content; (2) free Hb/heme, haptoglobin, hemopexin; and (3) urinary markers of AKI over the same time period. In addition, we developed a model system in Sprague–Dawley rats to test for AKI after intravenous injection of Exos Hb released during CPB. Results In 30 patients undergoing CPB, there is a significant increase in plasma Hb-positive Exos but not microvesicles 30 minutes post-XCR versus other time points, with a simultaneous decrease in the haptoglobin/Hb ratio. These changes presage a significant increase in urine neutrophil gelatinase–associated lipocalin and kidney injury molecule-1 at 24 hours. Intravenous injection of plasma Exos (109-10 particles obtained 30 minutes post-XCR) into rats causes AKI at 72 hours, manifested by multifocal degeneration of proximal tubular epithelium. At 21 days, there is persistent tubular injury and interstitial fibrosis. Intravenous injection of Exos from 35-day-old stored RBCs into rats results in glomerular–tubular injury, increased kidney ferritin and hemoxygenase-1 expression, and significant elevation of kidney injury molecule-1 and proteinuria at 72 hours. Conclusions These combined studies raise the potential for RBC-derived Exos, released during CPB, to target the kidney and mediate AKI. |
| Databáze: | OpenAIRE |
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