Inflammation, immunity, and hypertensive end-organ damage.
Inflammation, immunity, and hypertensive end-organ damage.
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DOI：
10.1161/circresaha.116.303697
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发表时间：
2015-03-13
影响因子：
20.1
通讯作者：
Harrison DG
中科院分区：
文献类型：
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作者：
McMaster WG;Kirabo A;Madhur MS;Harrison DG
50多年来，人们已经认识到免疫力有助于高血压。最近的数据已经确定了T细胞和各种T细胞衍生的细胞因子在几种实验性高血压模型中的重要作用。这些研究已经表明，刺激物如血管紧张素II、DOCA盐和过量的儿茶酚胺导致效应子样T细胞的形成，所述效应子样T细胞浸润肾脏和大动脉和小动脉的血管周围区域。在这些区域中还存在单核细胞/巨噬细胞的积聚。从这些细胞释放的细胞因子，包括IL-17、IFN-γ、TNFα和IL-6，促进肾和血管功能障碍和损伤，导致钠潴留增强和全身血管阻力增加。这些细胞因子对肾脏的影响尚不完全清楚，但包括血管紧张素原形成增强、钠重吸收增加和肾纤维化增加。最近的实验已经确定了高血压中氧化应激和免疫激活之间的联系。这些研究表明，高血压与树突细胞中活性氧的形成有关，活性氧导致γ-酮醛或异酮醛的形成。这些蛋白质迅速加合成赖氨酸，并由树突状细胞呈递为新抗原，激活T细胞并促进高血压。因此，先天性和适应性免疫系统的细胞都有助于高血压中的终末器官损伤和功能障碍。减少这些细胞活化的治疗干预可能证明有益于减少终末器官损伤和预防高血压的后果，包括心肌梗死、心力衰竭、肾衰竭和中风。
For more than 50 years, it has been recognized that immunity contributes to hypertension. Recent data have defined an important role of T cells and various T cell-derived cytokines in several models of experimental hypertension. These studies have shown that stimuli like angiotensin II, DOCA-salt and excessive catecholamines lead to formation of effector like T cells that infiltrate the kidney and perivascular regions of both large arteries and arterioles. There is also accumulation of monocyte/macrophages in these regions. Cytokines released from these cells, including IL-17, IFN-γ, TNFα and IL-6 promote both renal and vascular dysfunction and damage, leading to enhanced sodium retention and increased systemic vascular resistance. The renal effects of these cytokines remain to be fully defined, but include enhanced formation of angiotensinogen, increased sodium reabsorption and increased renal fibrosis. Very recent experiments have defined a link between oxidative stress and immune activation in hypertension. These have shown that hypertension is associated with formation of reactive oxygen species in dendritic cells that lead to formation of gamma ketoaldehydes, or isoketals. These rapidly adduct to protein lysines and are presented by dendritic cells as neoantigens that activate T cells and promote hypertension. Thus, cells of both the innate and adaptive immune system contribute to end-organ damage and dysfunction in hypertension. Therapeutic interventions to reduce activation of these cells may prove beneficial in reducing end-organ damage and preventing consequences of hypertension including myocardial infarction, heart failure, renal failure and stroke.