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The multifaceted role of ischemia/reperfusion in sickle cell anemia

机译:缺血/再灌注在镰状细胞性贫血中的多方面作用

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摘要

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.
机译: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。后者触发缺血/再灌注 (I/R) 病理生物学的一个版本,该病理生物学在其起源、周期性、复杂性、不稳定性、永久性和临床后果的广度方面是单一的。特定的临床特征可能归因于局部 I/R 损伤(例如卒中综合征)或远处器官损伤(例如急性胸部综合征)或炎症系统化(例如多灶性动脉病)。事实上,通过形成内皮功能障碍和脆弱性的潜在模板,强大的炎症系统化无疑有助于所有镰状病理学。在这篇综述中,我们重点介绍了 I/R 靶向疗法,这些疗法被证明可以改善接受 I/R 的镰状转基因小鼠的微血管血流,并建议如何将这些见解转化为人类治疗策略。

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