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MnSOD reduction causes mtDNA damage in HAEC under Oscillatory Shear Stress
Author(s) -
Quigley Katherine,
Fang Karen,
Jen Nelson,
Li Rongsong,
Hsiai Tzung
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1134.19
Subject(s) - mitochondrial dna , reactive oxygen species , dna damage , oxidative stress , superoxide dismutase , microbiology and biotechnology , shear stress , biology , dna , chemistry , gene , genetics , biochemistry , materials science , composite material
Fluid shear stress is intimately involved in vascular reactive oxygen species (ROS) production and inflammatory responses. While atheroprotective flow up‐regulates the expression of manganese superoxide dismutase (Mn‐SOD), atherogenic flow; namely, oscillatory shear stress (OSS) down‐regulates MnSOD. We hypothesize that OSS promotes mitochondrial DNA (mtDNA) via the down‐regulation of MnSOD. To simulate oscillatory shear stress at an arterial bifurcation, we exposed human aortic endothelial cells (HAEC) to a well‐defined flow profile (OSS at +/− 3 dynes/cm2) for 4 hours in a dynamic parallel flow system. MtDNA damage levels were quantified through amplification via PCR of the common 4,997‐bp deletion previously used as a DNA damage biomarker. Under these conditions, OSS increased mtDNA damage (p< 0.05, n=6). By the addition of an MnSOD mimetic, MnTMPγP, mitochondrial DNA damage was attenuated twofold (p<0.05, n=3). Further, in the presence of an MnSOD adenovirus, OSS‐induced mtDNA damage was also attenuated. Taken together, these results suggest that OSS induces vascular mtDNA damage via a reduction in MnSOD expression.