Targeting Arginine in COVID-19-Induced Immunopathology and Vasculopathy.
Targeting Arginine in COVID-19-Induced Immunopathology and Vasculopathy.
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DOI：
10.3390/metabo12030240
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发表时间：
2022-03-11
期刊：
影响因子：
4.1
通讯作者：
Durante W
中科院分区：
文献类型：
--
作者：
Durante W
2019冠状病毒病（COVID-19）是一场重大的公共卫生危机，已导致全球近600万人死亡。新出现的数据已经确定了COVID-19患者的循环精氨酸缺乏。精氨酸是一种半必需氨基酸，是免疫和血管细胞功能的关键调节剂。精氨酸被一氧化氮（NO）合酶代谢为NO，其在宿主防御和血管健康中起关键作用，而精氨酸被精氨酸酶催化为鸟氨酸有助于免疫抑制和血管疾病。值得注意的是，精氨酸酶活性在COVID-19患者中以疾病依赖性方式上调，有利于精氨酸产生鸟氨酸及其代谢产物，而不是NO的合成。COVID-19中精氨酸代谢的这种重新布线促进免疫和内皮细胞功能障碍，血管平滑肌细胞增殖和迁移，炎症，血管收缩，血栓形成，动脉增厚，纤维化和硬化，这可能导致血管闭塞、多器官衰竭和死亡。恢复精氨酸的血浆浓度、抑制精氨酸酶活性和/或增强NO的生物利用度和效力的策略代表了有希望的治疗方法，可以保护COVID-19患者的免疫功能并预防严重血管疾病的发展。
Coronavirus disease 2019 (COVID-19) represents a major public health crisis that has caused the death of nearly six million people worldwide. Emerging data have identified a deficiency of circulating arginine in patients with COVID-19. Arginine is a semi-essential amino acid that serves as key regulator of immune and vascular cell function. Arginine is metabolized by nitric oxide (NO) synthase to NO which plays a pivotal role in host defense and vascular health, whereas the catabolism of arginine by arginase to ornithine contributes to immune suppression and vascular disease. Notably, arginase activity is upregulated in COVID-19 patients in a disease-dependent fashion, favoring the production of ornithine and its metabolites from arginine over the synthesis of NO. This rewiring of arginine metabolism in COVID-19 promotes immune and endothelial cell dysfunction, vascular smooth muscle cell proliferation and migration, inflammation, vasoconstriction, thrombosis, and arterial thickening, fibrosis, and stiffening, which can lead to vascular occlusion, muti-organ failure, and death. Strategies that restore the plasma concentration of arginine, inhibit arginase activity, and/or enhance the bioavailability and potency of NO represent promising therapeutic approaches that may preserve immune function and prevent the development of severe vascular disease in patients with COVID-19.
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