{'fraction_non_alphanumeric': 0.02842227378190255, 'fraction_numerical': 0.011020881670533642, 'mean_word_length': 5.436567164179104, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Intravenous Glu-plasminogen attenuates cholesterol crystal embolism-induced thrombotic angiopathy, acute kidney injury and kidney infarction.

BACKGROUND
Cholesterol crystal (CC) embolism causes acute kidney injury (AKI) and ischemic cortical necrosis associated with high mortality. We speculated that sustaining the fibrinolytic system with Glu-plasminogen could be a safe way to attenuate AKI and to prevent ischemic infarction upon CC embolism.


METHODS
We induced CC embolism by injecting CC into the left kidney artery of C57BL/6J mice. The primary endpoint was glomerular filtration rate (GFR).


RESULTS
Starting as early as 2h after CC embolism, thrombotic angiopathy progressed gradually in interlobular, arcuate, and interlobar arteries. This was associated with a drop of GFR reaching a peak at 18h, i.e., AKI, and progressive ischemic kidney necrosis developing between 12-48h after CC injection. Human plasma Glu-plasminogen extracts injected intravenously 4h after CC embolism attenuated thrombotic angiopathy, GFR loss as well as ischemic necrosis in a dose-dependent manner. No bleeding complications occurred after Glu-plasminogen injection. Injection of an intermediate dose (0.6 mg/kg) had only a transient protective effect on microvascular occlusions lasting for a few hours without a sustained protective effect on AKI at 18-48h or cortical necrosis, while 1.5 mg/kg were fully protective. Importantly, no bleeding complications occurred.


CONCLUSIONS
These results provide the first experimental evidence that Glu-plasminogen could be an innovative therapeutic strategy to attenuate thrombotic angiopathy, AKI, kidney necrosis, and potentially other clinical manifestations of CC embolism syndrome.