The role of endothelial cell injury in thrombotic microangiopathy.
The role of endothelial cell injury in thrombotic microangiopathy.
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DOI：
10.1053/j.ajkd.2010.06.006
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发表时间：
2010-12
期刊：
影响因子：
--
通讯作者：
Thurman JM
中科院分区：
文献类型：
--
作者：
Goldberg RJ;Nakagawa T;Johnson RJ;Thurman JM
血栓性微血管病变（Thrombotic microangiopthy， TMA）是指内皮损伤导致血小板减少、微血管性溶血性贫血、肾损伤的一种临床病理综合征。许多病因可能诱发内皮损伤和TMA，包括肠道细菌毒素、补体调节蛋白的缺乏或功能障碍、血管性血友病因子切割蛋白酶的缺乏或抑制，以及抑制内皮细胞增殖和周转的因素。这使得专家们在设计治疗和管理方面专注于这些特定的诱发因素。然而，一个关键的和较少认识的因素是潜在的内皮健康水平。事实上，许多具有遗传病因的受试者可能多年无病，并且可能永远不会发病。其他急性刺激性事件，如大肠杆菌O157肠炎，从未表现出TMA。实验研究证明了特定因素的重要性，如内皮一氧化氮水平，有助于保护动物免受TMA的伤害。这表明，TMA的管理可能不仅仅是针对潜在的遗传原因或刺激事件的特定治疗，而是可以通过一般措施改善整体内皮健康。我们建议进行研究，以确定已知的改善内皮健康的干预措施，如ACE抑制剂、他汀类药物、维生素C、别嘌呤醇或产生一氧化氮的药物，是否能够预防TMA，即使是在具有潜在遗传条件的受试者中，这些条件本来会使他们易患这些疾病。
Thrombotic microangiopathy (TMA) refers to a clinical and pathological syndrome in which endothelial injury results in the manifestations of thrombocytopenia, microangiopathic hemolytic anemia, and renal injury. A host of etiologies may induce endothelial injury and TMA, including enteric bacterial toxins, deficiency or dysfunction of complement regulatory proteins, deficiency or inhibition of von Willebrand factor cleaving proteases, and factors that inhibit endothelial cell proliferation and turnover. This has led specialists to concentrate on these specific inciting factors in terms of designing treatment and management. However, a key and less recognized factor is the underlying level of endothelial health. Indeed, many subjects with hereditary etiologies may remain disease free for years, and may never develop disease. Others with acute inciting events such as E coli O157 enteritis never manifest TMA. Experimental studies document the importance of specific factors such as endothelial nitric oxide levels in helping to protect animals from TMA. This suggests that one might approach the management of TMA not simply with specific treatments aimed at the underlying hereditary cause or inciting event, but rather also at general measures that may improve overall endothelial health. We propose studies to determine if interventions known to improve endothelial health, such as the administration of ACE inhibitors, statins, vitamin C, allopurinol, or nitric oxide-producing drugs may be able to prevent TMA even in subjects with underlying hereditary conditions that would otherwise predispose them to these diseases.
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