Sickle cell anemia is a unique disease dominated by hemolytic anemia and vaso-occlusive events. The latter trigger a version of ischemia/reperfusion (I/R) pathobiology that is singular in its origin, cyclicity, complexity, instability, perpetuity, and breadth of clinical consequences. Specific clinical features are probably attributable to local I/R injury (e.g., stroke syndromes) or remote organ injury (e.g., acute chest syndrome) or the systematization of inflammation (e.g., multifocal arteriopathy). Indeed, by fashioning an underlying template of endothelial dysfunction and vulnerability, the robust inflammatory systematization no doubt contributes to all sickle pathology. In this Review, we highlight I/R-targeting therapeutics shown to improve microvascular blood flow in sickle transgenic mice undergoing I/R, and we suggest how such insights might be translated into human therapeutic strategies.

中文翻译：

---

缺血/再灌注在镰状细胞性贫血中的多方面作用。

镰状细胞性贫血是一种以溶血性贫血和血管闭塞事件为主的独特疾病。后者触发了一种形式的局部缺血/再灌注（I / R）病理生物学，其起源，周期性，复杂性，不稳定性，永续性和临床后果的范围都是单一的。具体的临床特征可能归因于局部I / R损伤（例如中风综合征）或远端器官损伤（例如急性胸腔综合征）或炎症的系统化（例如多灶性动脉病）。确实，通过形成内皮功能障碍和脆弱性的基础模板，强大的炎症系统化无疑会导致所有镰状病理。在这篇评论中，我们重点介绍了针对I / R的疗法，该疗法可改善接受I / R的镰状转基因小鼠的微血管血流量，