High glucose induced NF-κB DNA-binding activity in HAEC is maintained under low shear stress but inhibited under high shear stress: Role of nitric oxide

Sumathy Mohan, Masao Hamuro, Koichi Koyoma, George P. Sorescu, Hanjoong Jo, Mohan Natarajan

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

In the present study, we investigated whether low shear (LS, 2dyn/cm 2) favors high glucose (HG, 30mM) induced nuclear factor kappa B (NF-κB) activity by regulating NO release in human aortic endothelial cells (HAEC). The results show that (i) under LS, the NF-κB activity of HAEC exposed to HG was significantly higher than HAEC in normal glucose (NG, 5.5mM) (P<0.05). In contrast, under HS, the activation of NF-κB in HAEC exposed to HG showed no significant difference compared to that of NG. (ii) The NF-κB activity induced by HG is suppressed by high shear (HS) in the absence of a NO synthase inhibitor, Nω-nitro-L-arginine methyl ester (L-NAME) but restored in its presence, while LS+HG induced NF-κB activity remains the same in the presence or absence of L-NAME. (iii) Endothelial nitric oxide synthase (eNOS) protein expression and quantitative detection of NO indicated that high shear stress significantly induced higher eNOS expression and NO production compared to low shear stress condition. Collectively, these data suggest that HS exerts a protective effect on HG induced NF-κB activity through NO mediated signaling. LS, on the other hand, may down-regulate eNOS expression resulting in reduced NO release, and thereby maintain high glucose induced NF-κB DNA-binding activity. These observations explain, in part, the mechanism by means of which hyperglycemia accelerates the focal development of atherosclerotic lesions in low shear (lesion prone) areas of the arterial tree.

Original languageEnglish (US)
Pages (from-to)225-234
Number of pages10
JournalAtherosclerosis
Volume171
Issue number2
DOIs
StatePublished - Dec 2003

Keywords

  • Accelerated atherosclerosis
  • Diabetes mellitus
  • Hemodynamics
  • eNOS

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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