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.
|Journal||Free Radical Biology and Medicine|
|Volume||108, Supplement 1|
|Early online date||20 Jun 2017|
|Publication status||Published - 1 Jul 2017|
- Shear stress