High glucose induced NF-kappaB DNA-binding activity in HAEC is maintained under low shear stress but inhibited under high shear stress: role of nitric oxide.
In the present study, we investigated whether low shear (LS, 2 dyn/cm2) favors high glucose (HG, 30 mM) induced nuclear factor kappa B (NF-kappaB) activity by regulating NO release in human aortic endothelial cells (HAEC). The results show that (i) under LS, the NF-kappaB 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-kappaB in HAEC exposed to HG showed no significant difference compared to that of NG. (ii) The NF-kappaB activity induced by HG is suppressed by high shear (HS) in the absence of a NO synthase inhibitor, Nomega-nitro-L-arginine methyl ester (L-NAME) but restored in its presence, while LS + HG induced NF-kappaB 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-kappaB 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-kappaB 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.
Mohan
Sumathy
S
Department of Pathology, The University of Texas Health Science Center, San Antonio, TX 78229, USA. mohan@uthscsa.edu
Hamuro
Masao
M
Koyoma
Koichi
K
Sorescu
George P
GP
Jo
Hanjoong
H
Natarajan
Mohan
M
D000704:Analysis of Variance; D000818:Animals; D001011:Aorta; D001161:Arteriosclerosis / Q000503:physiopathology; D015153:Blotting, Western; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000503:physiopathology*; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D006943:Hyperglycemia / Q000503:physiopathology; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D011336:Probability; D011485:Protein Binding; D012680:Sensitivity and Specificity; D013314:Stress, Mechanical
D016328:NF-kappa B; D009569:Nitric Oxide; D005947:Glucose