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.

中文翻译：

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抑制补体因子 C5a 或 C5aR 治疗胆固醇晶体栓塞相关血管血栓形成伴微血管损伤及其后果


胆固醇晶体栓塞 （CCE） 意味着免疫血栓形成、组织坏死和器官衰竭，但没有可用的特异性治疗方法。由于 CCE 涉及补体激活，我们推测 C5a/C5aR 轴的抑制剂足以减轻 CCE 的后果，就像系统性血管炎一样。向野生型小鼠肾动脉注射胆固醇微晶，在数小时内引发肾内免疫血栓形成，随后 24 小时后肾小球滤过率突然下降，出现缺血性肾坏死。C3 或 C5aR 的遗传缺陷在 24 小时阻止了免疫血栓形成、肾小球滤过率下降和缺血性坏死，使用 C5a 或 C5aR 抑制剂进行抢先治疗也是如此。晶体注射后延迟 C5a 阻断仍可解决晶体凝块并防止所有后果。因此，选择性阻断 C5a 或 C5aR 足以减轻已建立的 CCE 的后果，并且对高危患者的前瞻性抑制在临床上可能是可行和安全的。