Abstract
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.
Highlights
Throughout the United States, systemic arterial hypertension and hypertension-related conditions, including coronary atherosclerotic heart disease and cerebrovascular disease, have disproportionate incidence, mortality, and morbidity among African Americans (AAs)
A follow-up analysis of these results identified that poly-(ADP-ribose) polymerase 1 (PARP-1), a DNA damage sensor protein involved in DNA
We sought to identify and validate novel hypertension-related targets for miR-1253, which was previously found to be significantly downregulated in peripheral blood mononuclear cells (PBMCs) of hypertensive African
Summary
Throughout the United States, systemic arterial hypertension and hypertension-related conditions, including coronary atherosclerotic heart disease and cerebrovascular disease, have disproportionate incidence, mortality, and morbidity among African Americans (AAs). Between 2013 and 2016, 66% of AA females over ≥20 years had hypertension, compared with 41.3%. Of non-Hispanic white women, 41% of Hispanic women, and 36% of Asian women [1]. Reducing or eliminating hypertension is predicted to reduce cardiovascular disease (CVD)-related mortality in. Genes 2020, 11, 572 women by almost 40% [1,2]. While 75% of AA women are aware of having hypertension, only 26%. Of AA women were able to control their high blood pressure [1]. A deeper understanding of the underlying biological mechanisms associated with hypertension may help reduce the burden of this condition
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