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Gene Expression Analysis of Endothelial Cells Exposed to Shear Stress Using Multiple Parallel-plate Flow Chambers
Published on: October 21, 2018
Shear stress influences spatial variations in vascular Mn-SOD expression: implication for LDL nitration
Lisong Ai1, Mahsa Rouhanizadeh, Joseph C Wu
1Department of Biomedical Engineering and Cardiovascular Medicine, University of Southern California, Los Angeles, CA 90089, USA.
American Journal of Physiology. Cell Physiology
|April 25, 2008
Summary
Pulsatile shear stress upregulates mitochondrial manganese superoxide dismutase (Mn-SOD) in atheroprotective regions, while oscillatory shear stress reduces it. This differential expression influences low-density lipoprotein (LDL) nitration, impacting vascular health.
Area of Science:
- Cardiovascular Biology
- Biophysics
- Molecular Biology
Background:
- Fluid shear stress is a critical regulator of vascular endothelial function, influencing key signaling molecules like superoxide anion (O2*-) and nitric oxide (*NO).
- The spatial distribution of mitochondrial manganese superoxide dismutase (Mn-SOD) in response to varying shear stress characteristics within vasculatures remains incompletely understood.
Purpose of the Study:
- To investigate how different types of shear stress, pulsatile (PSS) and oscillatory (OSS), affect the spatial expression of mitochondrial Mn-SOD in arterial bifurcations.
- To determine the functional consequence of differential Mn-SOD expression on low-density lipoprotein (LDL) nitration in vascular regions exposed to varying shear stress patterns.
Main Methods:
- A three-dimensional computational fluid dynamics model was used to simulate shear stress distribution at arterial bifurcations.
- Immunohistolocalization was performed on human arterial bifurcation explants to assess Mn-SOD expression.
- Cultured bovine aortic endothelial cells were subjected to controlled PSS and OSS conditions to measure Mn-SOD mRNA levels.
- Liquid chromatography and tandem mass spectrometry analyzed LDL nitration levels.
- Small interfering RNA (siRNA) targeting Mn-SOD was used to evaluate its role in nitrotyrosine formation.
Main Results:
- Mn-SOD expression was significantly higher in regions exposed to PSS (atheroprotective) compared to regions with OSS (atheroprone).
- PSS upregulated Mn-SOD mRNA expression more effectively than OSS in cultured endothelial cells.
- PSS reduced LDL nitration, whereas OSS increased it.
- Inhibition of Mn-SOD activity exacerbated nitrotyrosine formation in the presence of LDL.
Conclusions:
- Shear stress patterns differentially regulate spatial Mn-SOD expression in vascular regions, with higher expression in atheroprotective PSS zones.
- The observed variations in Mn-SOD expression play a role in modulating LDL nitration, suggesting a mechanism linking mechanical forces to oxidative stress and vascular disease development.
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