The prevalence of hypertension among African Americans (AAs) in the US is among the highest of any demographic and affects over two-thirds of AA women. Previous data from our laboratory suggest substantial differential gene expression (DGE) of mRNAs and microRNAs (miRNAs) exists within peripheral blood mononuclear cells (PBMCs) isolated from AA and white women with or without hypertension. We hypothesized that DGE by race may contribute to racial differences in hypertension. In a reanalysis of our previous dataset, we found that the Wiskott–Aldrich syndrome protein Verprolin-homologous protein 2 (WASF2 (also known as WAVE2)) is differentially expressed in AA women with hypertension, along with several other members of the actin cytoskeleton signaling pathway that plays a role in cell shape and branching of actin filaments. We performed an in silico miRNA target prediction analysis that suggested miRNA miR-1253 regulates WASF2. Transfection of miR-1253 mimics into human umbilical vein endothelial cells (HUVECs) and human aortic endothelial cells (HAECs) significantly repressed WASF2 mRNA and protein levels (p < 0.05), and a luciferase reporter assay confirmed that miR-1253 regulates the WASF2 3′ UTR (p < 0.01). miR-1253 overexpression in HUVECs significantly increased HUVEC lamellipodia formation (p < 0.01), suggesting the miR-1253–WASF2 interaction may play a role in cell shape and actin cytoskeleton function. Together, we have identified novel roles for miR-1253 and WASF2 in a hypertension-related disparities context. This may ultimately lead to the discovery of additional actin-related genes which are important in the vascular-related complications of hypertension and influence the disproportionate susceptibility to hypertension among AAs in general and AA women in particular.

中文翻译：

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MicroRNA-1253 WASF2 (WAVE2) 的调控及其与种族健康差异的相关性


美国非裔美国人 (AA) 的高血压患病率是所有人群中最高的，影响了超过三分之二的 AA 女性。我们实验室之前的数据表明，从 AA 和患有或不患有高血压的白人女性中分离出的外周血单核细胞 (PBMC) 中存在 mRNA 和 microRNA (miRNA) 的显着差异基因表达 (DGE)。我们假设不同种族的 DGE 可能会导致高血压的种族差异。在对之前数据集的重新分析中，我们发现 Wiskott-Aldrich 综合征蛋白 Verprolin 同源蛋白 2（WASF2（也称为 WAVE2））以及肌动蛋白细胞骨架信号传导的其他几个成员在患有高血压的 AA 女性中差异表达在细胞形状和肌动蛋白丝分支中发挥作用的途径。我们进行了计算机模拟 miRNA 靶标预测分析，表明 miRNA miR-1253 调节 WASF2。将 miR-1253 模拟物转染人脐静脉内皮细胞 (HUVEC) 和人主动脉内皮细胞 (HAEC) 显着抑制 WASF2 mRNA 和蛋白质水平 (p < 0.05)，并且荧光素酶报告基因检测证实 miR-1253 调节 WASF2 3 ′ UTR（p < 0.01）。 HUVEC 中 miR-1253 的过表达显着增加了 HUVEC 板状伪足的形成 (p < 0.01)，表明 miR-1253-WASF2 相互作用可能在细胞形状和肌动蛋白细胞骨架功能中发挥作用。我们共同确定了 miR-1253 和 WASF2 在高血压相关差异背景中的新作用。 这可能最终导致发现额外的肌动蛋白相关基因，这些基因在高血压的血管相关并发症中很重要，并影响一般 AA（尤其是 AA 女性）对高血压的不成比例的易感性。