P 057 - Mechanosensitive microRNAS in endothelial responses to shear stress and Nrf2-mediated redox signalling: Abstracts of the OCC World Congress and Annual SFRR-E Conference 2017 Metabolic Stress and Redox Regulation Berlin, Germany 21-23 June 2017

TY - JOUR

T1 - P 057 - Mechanosensitive microRNAS in endothelial responses to shear stress and Nrf2-mediated redox signalling

T2 - Abstracts of the OCC World Congress and Annual SFRR-E Conference 2017 Metabolic Stress and Redox Regulation Berlin, Germany 21-23 June 2017

AU - Kitscha, Phoebe

AU - Mann, Giovanni E

AU - Siow, Richard C

PY - 2017/7/1

Y1 - 2017/7/1

N2 - Atherosclerotic lesions develop in regions of the vasculature with complex fluid shear stress (FSS) patterns. Endothelial cells (EC) in atheroprone and atheroprotected regions are exposed to low oscillatory (OS) or high unidirectional (US) shear stresses respectively. Oxidative stress and altered activity of the transcription factor Nrf2 have been shown to contribute to atherogenesis. Using in vitro culture of human umbilical vein EC (HUVEC) under FSS, we have confirmed that expression and nuclear translocation of Nrf2 are enhanced by US (15 dyn/cm2) compared with OS (±5 dyn/cm2), enhancing expression of antioxidant genes such as heme oxygenase-1 (HO-1) and glutathione levels. This study investigates whether mechanosensitive microRNAs may contribute to FSS-dependent Nrf2 regulation. A screen of microRNAs known or predicted to target antioxidant genes revealed that microRNAs miR-21-3p, miR-320a, and miR-409-5p are significantly differentially regulated in HUVEC exposed to OS or US for 24 hours. Overexpression of miR-320a in static HUVEC using miRNA mimics significantly enhanced protein expression of HO-1, recapitulating observations in EC under US. This study suggests that modulation of microRNAs may ameliorate deficits in redox signalling in EC under atheroprone FSS.

AB - Atherosclerotic lesions develop in regions of the vasculature with complex fluid shear stress (FSS) patterns. Endothelial cells (EC) in atheroprone and atheroprotected regions are exposed to low oscillatory (OS) or high unidirectional (US) shear stresses respectively. Oxidative stress and altered activity of the transcription factor Nrf2 have been shown to contribute to atherogenesis. Using in vitro culture of human umbilical vein EC (HUVEC) under FSS, we have confirmed that expression and nuclear translocation of Nrf2 are enhanced by US (15 dyn/cm2) compared with OS (±5 dyn/cm2), enhancing expression of antioxidant genes such as heme oxygenase-1 (HO-1) and glutathione levels. This study investigates whether mechanosensitive microRNAs may contribute to FSS-dependent Nrf2 regulation. A screen of microRNAs known or predicted to target antioxidant genes revealed that microRNAs miR-21-3p, miR-320a, and miR-409-5p are significantly differentially regulated in HUVEC exposed to OS or US for 24 hours. Overexpression of miR-320a in static HUVEC using miRNA mimics significantly enhanced protein expression of HO-1, recapitulating observations in EC under US. This study suggests that modulation of microRNAs may ameliorate deficits in redox signalling in EC under atheroprone FSS.

KW - Shear stress

KW - microRNAs

KW - Nrf2

U2 - 10.1016/j.freeradbiomed.2017.04.142

DO - 10.1016/j.freeradbiomed.2017.04.142

M3 - Meeting abstract

SN - 0891-5849

VL - 108, Supplement 1

SP - S37

JO - Free Radical Biology and Medicine

JF - Free Radical Biology and Medicine

ER -