Mineralocorticoid Receptor in Myeloid Cells Mediates Angiotensin II-Induced Vascular Dysfunction in Female Mice.
Mineralocorticoid Receptor in Myeloid Cells Mediates Angiotensin II-Induced Vascular Dysfunction in Female Mice.
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DOI：
10.3389/fphys.2021.588358
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发表时间：
2021
影响因子：
4
通讯作者：
Lastra G
中科院分区：
文献类型：
--
作者：
Manrique-Acevedo C;Padilla J;Naz H;Woodford ML;Ghiarone T;Aroor AR;Hulse JL;Cabral-Amador FJ;Martinez-Diaz V;Hans CP;Whaley-Connell A;Martinez-Lemus LA;Lastra G
增强的盐皮质激素受体（MR）信号传导对内皮功能障碍和动脉硬化的发展至关重要。然而，目前对MR诱导的脂肪组织炎症在女性血管功能障碍发生中的作用缺乏了解。在这项研究中，我们假设髓系细胞中的MR激活通过增加促炎（M1）巨噬细胞极化导致血管紧张素II（Ang II）诱导的女性主动脉硬化和内皮功能障碍。用Ang II（500 ng/kg/min）输注骨髓细胞中缺乏MR的雌性小鼠（MyMRKO）4周。随后测定主动脉僵硬度和血管反应，以及测量不同脂肪组织隔室中炎症和巨噬细胞浸润/极化的标志物。MyMRKO小鼠保护血管紧张素II诱导的主动脉内皮硬化，通过原子力显微镜评估主动脉外植体，血管舒张功能障碍，通过主动脉丝肌造影。在对齐，MyMRKO小鼠保护免受血管紧张素II诱导的巨噬细胞浸润和M1极化内脏脂肪组织（VAT）和胸部血管周围脂肪组织（tPVAT）。总的来说，本研究证明了骨髓细胞中MR活化在VAT和tPVAT中与促炎性巨噬细胞极化相关的女性血管功能障碍发病机制中的关键作用。我们的数据对预防和管理女性心血管疾病具有潜在的临床意义，女性心血管疾病的风险较高，预后不良。
Enhanced mineralocorticoid receptor (MR) signaling is critical to the development of endothelial dysfunction and arterial stiffening. However, there is a lack of knowledge about the role of MR-induced adipose tissue inflammation in the genesis of vascular dysfunction in women. In this study, we hypothesize that MR activation in myeloid cells contributes to angiotensin II (Ang II)-induced aortic stiffening and endothelial dysfunction in females via increased pro-inflammatory (M1) macrophage polarization. Female mice lacking MR in myeloid cells (MyMRKO) were infused with Ang II (500 ng/kg/min) for 4 weeks. This was followed by determinations of aortic stiffness and vasomotor responses, as well as measurements of markers of inflammation and macrophage infiltration/polarization in different adipose tissue compartments. MyMRKO mice were protected against Ang II-induced aortic endothelial stiffening, as assessed via atomic force microscopy in aortic explants, and vasorelaxation dysfunction, as measured by aortic wire myography. In alignment, MyMRKO mice were protected against Ang II-induced macrophage infiltration and M1 polarization in visceral adipose tissue (VAT) and thoracic perivascular adipose tissue (tPVAT). Collectively, this study demonstrates a critical role of MR activation in myeloid cells in the pathogenesis of vascular dysfunction in females associated with pro-inflammatory macrophage polarization in VAT and tPVAT. Our data have potential clinical implications for the prevention and management of cardiovascular disease in women, who are disproportionally at higher risk for poor outcomes.
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影响因子：
14.5
作者：
Cho, Ik-Hyun;Hong, Jinpyo;Lee, Sung Joong
通讯作者：
Lee, Sung Joong
影响因子：
7.7
作者：
Cat, Aurelie Nguyen Dinh;Antunes, Tayze T.;Touyz, Rhian M.
通讯作者：
Touyz, Rhian M.
西地那非恢复载脂蛋白E基因敲除小鼠中的内皮功能。
影响因子：
7.4
作者：
Balarini CM;Leal MA;Gomes IB;Pereira TM;Gava AL;Meyrelles SS;Vasquez EC
通讯作者：
Vasquez EC
DOI：
10.1161/atvbaha.114.303029
发表时间：
2014-08
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Brown NK;Zhou Z;Zhang J;Zeng R;Wu J;Eitzman DT;Chen YE;Chang L
通讯作者：
Chang L
DOI：
10.1073/pnas.0503878102
发表时间：
2006-01-03
影响因子：
11.1
作者：
Berger, S;Wolfer, DP;Schütz, G
通讯作者：
Schütz, G