Are macrophages the foot soldiers in the war waged by aldosterone against the heart?
Are macrophages the foot soldiers in the war waged by aldosterone against the heart?
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巨噬细胞是醛固酮对心脏发动的战争中的步兵吗？
DOI：
10.1161/hypertensionaha.109.135855
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Dorrance,AnneM
中科院分区：
文献类型：
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作者：
Dorrance,AnneM
盐皮质激素受体（MR）存在于无数的肾外组织中，包括内皮细胞、血管平滑肌细胞和心肌细胞。[2] MR在这些组织中所起的生理作用尚不清楚，因为到目前为止，醛固酮似乎只对这些受体产生有害作用。Rickard等人的研究3将巨噬细胞添加到醛固酮具有病理生理作用的细胞列表中。这个小组已经表明，醛固酮，或MR激活，是内在地参与心脏纤维化和炎症和巨噬细胞浸润的前兆。4，5最新的文章强调了巨噬细胞在这一过程中的重要性，并将巨噬细胞中的MR分配为关键角色（图）。这项优雅的研究使用了巨噬细胞特异性MR敲除小鼠。当用脱氧皮质酮（DOC）处理时，野生型小鼠发展高血压、心脏纤维化和伴随巨噬细胞浸润的炎症。敲除小鼠显示巨噬细胞浸润，但不发展纤维化或高血压。这告诉我们两件事。首先，巨噬细胞可以浸润组织而没有有害影响。第二，巨噬细胞MR需要介导血压和纤维化反应，但不需要浸润。这只是故事的一面。当考虑到渗透过程时，醛固酮在炎症反应中所起的作用变得复杂。Rickard等人3的研究表明，巨噬细胞MR对控制浸润作用不大。然而，Caprio等人1的研究表明，MR激活仅在不同的细胞类型中起关键作用。这个小组显示醛固酮增加内皮细胞上细胞内粘附分子1的表达;细胞内粘附分子1是巨噬细胞附着于内皮所必需的。因此，似乎MR激活负责确保巨噬细胞到达适当的目的地并控制其到达时的活动。
The mineralocorticoid receptor (MR) is present in a myriad of extrarenal tissues, including endothelial cells, 1 vascular smooth muscle cells, and cardiac myocytes. 2 The physiological role played by the MR in these tissues remains unclear because, as yet, aldosterone seems to have only deleterious effects at these receptors. The study by Rickard et al3 adds macrophages to the list of cells where aldosterone has pathophysiological effects. This group has shown that aldosterone, or MR activation, is intrinsically involved in cardiac fibrosis and that inflammation and macrophage infiltration are precursors to this. 4, 5 The latest article highlights the importance of macrophages in this process and assigns a key role to the MR in macrophages (Figure). This elegant study used macrophage-specific MR knockout mice. When treated with deoxycorticosterone (DOC), wild-type mice develop hypertension, cardiac fibrosis, and inflammation concomitant to macrophage infiltration. Knockout mice show macrophage infiltration but do not develop fibrosis or hypertension. This tells us 2 things. First, macrophages may infiltrate a tissue without having detrimental effects. Second, the macrophage MR is needed to mediate the blood pressure and fibrogenic responses but not for infiltration. That is only one side of the story. The role played by aldosterone in the inflammatory response becomes complicated when one considers the infiltration process. The study by Rickard et al3 suggests the macrophage MR does little to control infiltration. However, studies by Caprio et al1 suggest that MR activation plays a key role, just in a different cell type. This group showed that aldosterone increases intracellular adhesion molecule 1 expression on endothelial cells; intracellular adhesion molecule 1 is required for macrophage attachment to the endothelium. Therefore, it appears that MR activation is responsible for both ensuring that the macrophages get to the appropriate destination and for controlling their activities on arrival.