Neutrophil circadian rhythm is associated with different outcomes of acute kidney injury due to cholesterol crystal embolism

Shi, Chongxu; Zhao, Danyang; Lyubenov, Lyuben; Motrapu, Manga; Li, Na; Steiger, Stefanie; Mammadova-Bach, Elmina; Yang, Luying; Liu, Dong; Anders, Hans-Joachim (2022): Neutrophil circadian rhythm is associated with different outcomes of acute kidney injury due to cholesterol crystal embolism. Frontiers in Cardiovascular Medicine, 9. ISSN 2297-055X

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.

• Doc-Type: Article (LMU Hospital)
• Organisational unit (Faculties): 07 Medicine > Medical Center of the University of Munich > Medical Clinic and Outpatient Clinic IV (Endocrinology, nephrology, other sections)
• DFG subject classification of scientific disciplines: Life sciences
• DFG: Funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) - 449437943
• DFG: Funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) - 491502892