Abstract
Cholesterol crystal (CC) embolism can cause acute tissue infarction and ischemic necrosis via triggering diffuse thrombotic angiopathy occluding arterioles and arteries. Neutrophils contribute to crystal-induced immunothrombosis as well as to ischemic necrosis-related necroinflammation. We speculated that CC embolism-induced acute kidney injury (AKI) would be circadian rhythm-dependent and associated with cyclic differences in neutrophil function. Injection of CC into the left kidney induced thrombotic angiopathy progressing starting as early as 3 h after CC injection followed by a progressive ischemic cortical necrosis and AKI at 24 h. In C57BL/6J mice, circulating CD11b+Ly6G+ neutrophils were higher during the day phase [Zeitgeber time (ZT) 0–12] compared to the dark phase (ZT12-24). In the time frame of thrombus formation at ZT13, more neutrophils were recruited into the injured kidney 24 h later compared to CC embolism at ZT5. This effect was associated with an increased circulating number of CXCR2+ neutrophils as well as an upregulated kidney adhesion molecule and chemokine expression. These findings were associated with a significant increase in kidney necrosis, and endothelial injury at ZT13. Thus, the time of day has an effect also on CC embolism-related AKI in association with the circadian rhythm of neutrophil recruitment.
| Dokumententyp: | Zeitschriftenartikel |
|---|---|
| Fakultät: | Medizin > Klinikum der LMU München > Medizinische Klinik und Poliklinik IV (Endokrinologie, Nephrologie, weitere Sektionen) |
| Themengebiete: | 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit |
| ISSN: | 2297-055X |
| Sprache: | Englisch |
| Dokumenten ID: | 104577 |
| Datum der Veröffentlichung auf Open Access LMU: | 13. Jul. 2023, 13:42 |
| Letzte Änderungen: | 24. Aug. 2023, 14:44 |
| DFG: | Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 491502892 |
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