Discipline: Biological Sciences
Subcategory: Cell and Molecular Biology
Room: Exhibit Hall A
Mercy Arkorful - Morgan State University
Co-Author(s): Nicole Noren Hooten, Laboratory of Epidemiology and Population Science, National Institute on Aging, NIH, Baltimore, MD; Amirah N. Hewitt, Laboratory of Epidemiology and Population Science, National Institute on Aging, NIH, Baltimore, MD; Lori Barrientos Sanchez, Laboratory of Epidemiology and Population Science, National Institute on Aging, NIH, Baltimore, MD; Yongqing Zhang, Laboratory of Genetics and Genomics, National Institute on Aging, NIH, Baltimore, MD; Michele K. Evans, Laboratory of Epidemiology and Population Science, National Institute on Aging, NIH, Baltimore, MD; Douglas F. Dluzen, Department of Biology, Morgan State University, Baltimore, MD
Hypertension in African Americans (AAs) in the US is among the highest in the world and almost 50% of AA women have high blood pressure. Previous data from our laboratory suggest that differential gene expression (DGE) of mRNAs and microRNAs (miRNAs) in peripheral blood mononuclear cells (PBMCs) isolated from AA and white women with or without hypertension were involved in hypertension-related pathways. Our goal is to understand how DGE patterns by race may contribute to racial differences in hypertension. We found that the Wiskott-Aldrich syndrome protein verprolin homologous-2 (WAVE2) was differentially-expressed in AA women with hypertension. Wiskott-Aldrich syndrome proteins are actin-regulating proteins that include WAVE2 (also referred to WASF2) and play a role in signaling to the actin cytoskeleton, which influences changes in cell shape or function. We hypothesized that differentially-expressed miRNAs contribute to WAVE2 expression patterns in AA women with hypertension and may play a role in actin cytoskeleton function. In silico miRNA target prediction with DIANA TarBase and Target Scan predicted that the miRNA miR-1253 potentially targets WAVE2. Transfection of miR-1253 mimics into HUVECs and HAECs significantly repressed WAVE2 mRNA and protein levels (P<0.05; n=3-5), confirming miR-1253 regulates WAVE2 expression. Confirmation was determined via a luciferase assay, where it was discovered that luciferase activity was significantly reduced in HUVECs where mir-1253 was overexpressed. To assess changes on the actin cytoskeleton, miR-1253 overexpression in HUVEs significantly increased lamellipodia, an actin enriched projection at the leading edge of a cell. There was no change in cellular filopodia and there was a non-significant increase in cell area (n=3). Discovery of additional miRNAs which are involved in racially disparate diseases will provide more options for treatment and help to combat hypertension disparities, particularly in communities most at risk.
Funder Acknowledgement(s): NIA Intramural Research Program (AG000519); NIGMS RISE #R25GM058904; NIGMS ASCEND #TL4GM118974;NIMHD RCMI@Morgan #U54MD013367-8281.
Faculty Advisor: Douglas Dluzen, Douglas.Dluzen@morgan.edu
Role: I performed the transfections of the HUVECs, both with the miR-1253 mimic, and the scrambled control. I performed the immunoblot that confirmed the changes in protein expression. I also performed the luciferase assay. I stained the HUVECs with rhodamine phalloidin to asses the actin cytoskeleton, and calculated the average area of the cells to identify any possible differences.