Inhibition of complement factor C5a or C5aR for cholesterol crystal embolism–related vascular thrombosis with microvascular injury and its consequences

作者：Danyang Zhao, Chao Han, Elmina Mammadova‐Bach, Kanako Watanabe‐Kusunoki, Tâmisa Seeko Bandeira Honda, Yihong Li, Chenyu Li, Qiubo Li, Hao Long, Lyuben Lyubenov, Chongxu Shi, Donato Santovito, Christian Weber, Peter Boor, Patrick Droste, Samir V. Parikh, John P. Shapiro, Letizia De Chiara, Giulia Carangelo, Paola Romagnani, Sven Klußmann, Kai Hoehlig, Axel Vater, Hans‐Joachim Anders · 发表于：Kidney International · 年份：2024 · DOI：10.1016/j.kint.2024.07.020 · 被引用次数：13 · 研究领域：Aortic Thrombus and Embolism、Vasculitis and related conditions、Cardiac tumors and thrombi

Cholesterol crystal embolism (CCE) implies immunothrombosis, tissue necrosis, and organ failure but no specific treatments are available. As CCE involves complement activation, we speculated that inhibitors of the C5a/C5aR axis would be sufficient to attenuate the consequences of CCE like that with systemic vasculitis. Cholesterol microcrystal injection into the kidney artery of wild-type mice initiated intra-kidney immunothrombosis within a few hours followed by a sudden drop of glomerular filtration rate and ischemic kidney necrosis after 24 hours. Genetic deficiency of either C3 or C5aR prevented immunothrombosis, glomerular filtration rate drop, and ischemic necrosis at 24 hours as did preemptive treatment with inhibitors of either C5a or C5aR. Delayed C5a blockade after crystal injection still resolved crystal clots and prevented all consequences. Thus, selective blockade of C5a or C5aR is sufficient to attenuate the consequences of established CCE and prospective inhibition in high-risk patients may be clinically feasible and safe.