Oscillatory Shear Stress Stimulates Endothelial Production of O 2- from p47phox-dependent NAD(P)H Oxidases, Leading to Monocyte Adhesion

Jinah Hwang, Aniket Saha, Yong Chool Boo, George P. Sorescu, J. Scott McNally, Steven M. Holland, Sergei Dikalov, Don P. Giddens, Kathy K. Griendling, David G. Harrison, Hanjoong Jo

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262 Scopus citations

Abstract

Arterial regions exposed to oscillatory shear (OS) in branched arteries are lesion-prone sites of atherosclerosis, whereas those of laminar shear (LS) are relatively well protected. Here, we examined the hypothesis that OS and LS differentially regulate production of O2- from the endothelial NAD(P)H oxidase, which, in turn, is responsible for their opposite effects on a critical atherogenic event, monocyte adhesion. We used aortic endothelial cells obtained from C57BL6 (MAE-C57) and p47phox-/- (MAE-p47-/-) mice, which lack a component of NAD(P)H oxidase. O 2- production was determined by dihydroethidium staining and an electron spin resonance using an electron spin trap methoxycarbonyl-2,2,5,5-tetramethyl-pyrrolidine. Chronic exposure (18 h) to an arterial level of OS (± 5 dynes/cm2) increased O 2- (2-fold) and monocyte adhesion (3-fold) in MAE-C57 cells, whereas chronic LS (15 dynes/cm2, 18 h) significantly decreased both monocyte adhesion and O2- compared with static conditions. In contrast, neither LS nor OS were able to induce O 2- production and monocyte adhesion to MAE-p47 -/-. Treating MAE-C57 with a cell-permeable superoxide dismutase compound, polyethylene glycol-superoxide dismutase, also inhibited OS-induced monocyte adhesion. In addition, over-expressing p47phox in MAE -/-p47-/- restored OS-induced O2- production and monocyte adhesion. These results suggest that chronic exposure of endothelial cells to OS stimulates O2- and/or its derivatives produced from p47phox-dependent NAD(P)H oxidase, which, in turn, leads to monocyte adhesion, an early and critical atherogenic event.

Original languageEnglish
Pages (from-to)47291-47298
Number of pages8
JournalJournal of Biological Chemistry
Volume278
Issue number47
DOIs
StatePublished - 21 Nov 2003

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