Shear stress influences spatial variations in vascular Mn-SOD expression: implication for LDL nitration

Lisong Ai; Mahsa Rouhanizadeh; Joseph C Wu; Wakako Takabe; Hongyu Yu; Mohammad Alavi; Rongsong Li; Yi Chu; Jordan Miller; Donald D Heistad; Tzung K Hsiai

doi:10.1152/ajpcell.00518.2007

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Shear stress influences spatial variations in vascular Mn-SOD expression: implication for LDL nitration

Journal article

Open access

Peer reviewed

Shear stress influences spatial variations in vascular Mn-SOD expression: implication for LDL nitration

Lisong Ai, Mahsa Rouhanizadeh, Joseph C Wu, Wakako Takabe, Hongyu Yu, Mohammad Alavi, Rongsong Li, Yi Chu, Jordan Miller, Donald D Heistad, …

American Journal of Physiology: Cell Physiology, Vol.294(6), pp.C1576-1585

06/2008

DOI: 10.1152/ajpcell.00518.2007

PMCID: PMC3008554

PMID: 18434620

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Abstract

Fluid shear stress modulates vascular production of endothelial superoxide anion (O2*-) and nitric oxide (*NO). Whether the characteristics of shear stress influence the spatial variations in mitochondrial manganese superoxide dismutase (Mn-SOD) expression in vasculatures is not well defined. We constructed a three-dimensional computational fluid dynamics model simulating spatial variations in shear stress at the arterial bifurcation. In parallel, explants of arterial bifurcations were sectioned from the human left main coronary bifurcation and right coronary arteries for immunohistolocalization of Mn-SOD expression. We demonstrated that Mn-SOD staining was prominent in the pulsatile shear stress (PSS)-exposed and atheroprotective regions, but it was nearly absent in the oscillatory shear stress (OSS)-exposed regions and lateral wall of arterial bifurcation. In cultured bovine aortic endothelial cells, PSS at mean shear stress (tau ave) of 23 dyn/cm2 upregulated Mn-SOD mRNA expression at a higher level than did OSS at tau ave = 0.02 dyn/cm2 +/- 3.0 dyn.cm(-2).s(-1) and at 1 Hz (PSS by 11.3 +/- 0.4-fold vs. OSS by 5.0 +/- 0.5-fold vs. static condition; P < 0.05, n = 4). By liquid chromatography and tandem mass spectrometry, it was found that PSS decreased the extent of low-density lipoprotein (LDL) nitration, whereas OSS increased nitration (P < 0.05, n = 4). In the presence of LDL, treatment with Mn-SOD small interfering RNA increased intracellular nitrotyrosine level (P < 0.5, n = 4), a fingerprint for nitrotyrosine formation. Our findings indicate that shear stress in the atheroprone versus atheroprotective regions regulates spatial variations in mitochondrial Mn-SOD expression with an implication for modulating LDL nitration.

Immunohistochemistry

Superoxide Dismutase - genetics

Pulsatile Flow

Humans

Stress, Mechanical

Chromatography, High Pressure Liquid

Hemorheology

RNA, Messenger - metabolism

Tyrosine - analogs & derivatives

Coronary Vessels - metabolism

Tandem Mass Spectrometry

Atherosclerosis - enzymology

RNA Interference

Cattle

Computer Simulation

Lipoproteins, LDL - metabolism

Cell Culture Techniques

Superoxide Dismutase - metabolism

Coronary Vessels - enzymology

Endothelial Cells - metabolism

Models, Cardiovascular

Tissue Culture Techniques

Cells, Cultured

Atherosclerosis - metabolism

Tyrosine - metabolism

Animals

Endothelial Cells - enzymology

Details

Title: Subtitle: Shear stress influences spatial variations in vascular Mn-SOD expression: implication for LDL nitration
Creators: Lisong Ai - Department of Biomedical Engineering and Cardiovascular Medicine, University of Southern California, Los Angeles, CA 90089, USA
Mahsa Rouhanizadeh
Joseph C Wu
Wakako Takabe
Hongyu Yu
Mohammad Alavi
Rongsong Li
Yi Chu
Jordan Miller
Donald D Heistad
Tzung K Hsiai
Resource Type: Journal article
Publication Details: American Journal of Physiology: Cell Physiology, Vol.294(6), pp.C1576-1585
DOI: 10.1152/ajpcell.00518.2007
PMID: 18434620
PMCID: PMC3008554
NLM abbreviation: Am J Physiol Cell Physiol
ISSN: 0363-6143
eISSN: 1522-1563
Publisher: United States
Grant note: HL-083015 / NHLBI NIH HHS R01 HL083015-04 / NHLBI NIH HHS K08 HL068689-04 / NHLBI NIH HHS K08 HL068689 / NHLBI NIH HHS R01 HL118650 / NHLBI NIH HHS HL-068689 / NHLBI NIH HHS R01 HL083015 / NHLBI NIH HHS
Language: English
Date published: 06/2008
Academic Unit: Cardiovascular Medicine; Neuroscience and Pharmacology; Internal Medicine
Record Identifier: 9984040335802771

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