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Dluzen, D. F.

Publications and source records attributed to Dluzen, D. F..

2 recordsLinked to original sources

Poverty shapes the transcriptome of immune cells

Social factors influence health outcomes and life expectancy. Individuals living in poverty often have adverse health outcomes related to chronic inflammation that affect the cardiovascular, renal, and pulmonary systems. Negative psychosocial experiences are associated with transcriptional changes in genes associated with complex traits. However, the underlying molecular mechanisms by which poverty increases the risk of disease and health disparities are still not fully understood. To bridge the gap in our understanding of the link between living in poverty and adverse health outcomes, we performed RNA sequencing of blood immune cells from 204 participants of the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study in Baltimore, Maryland. We identified 138 genes differentially expressed in association with poverty. Genes differentially expressed were enriched in wound healing and coagulation processes. Of the genes differentially expressed in individuals living in poverty, EEF1DP7 and VIL1 are also associated with hypertension in transcriptome-wide association studies. Our results suggest that living in poverty influences inflammation and the risk for cardiovascular disease through gene expression changes in immune cells.

genomics↗

MicroRNA 1253 regulation of WAVE2 and its relevance to health disparities in hypertension

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 suggests 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. We found that the Wiskott-Aldrich syndrome protein Verprolin homologous-2 (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 WAVE2. Transfection of miR-1253 mimics into human umbilical vein endothelial cells (HUVECs) and human aortic endothelial cells (HAECs) significantly repressed WAVE2 mRNA and protein levels (P<0.05), and a luciferase reporter assay confirmed that miR-1253 regulates the WAVE2 3 UTR (P<0.01). miR-1253 over-expression in HUVECs significantly increased HUVEC lamellipodia formation (P<0.01), suggesting the miR-1253/WAVE2 interaction may play a role in endothelial cell shape and actin cytoskeleton function. Together, we have identified novel roles for miR-1253 and WAVE2 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.

cell biology↗