Abstract

Endothelial activation and subsequent recruitment of inflammatory cells are important steps in atherogenesis. The increased levels of cell adhesion molecules (CAM) have been identified in diabetic vasculatures, but the underlying mechanisms remain unclear. To determine the relationship among vascular production of superoxide, expression of CAM and diabetes, superoxide generation and expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E- and P-selectin in the aorta from control (C57BL/6J) and diabetic mice (ob/ob) were measured. In situ staining for superoxide using dihydroethidium showed an increased superoxide production in diabetic aorta, accompanied with an enhanced NAD(P)H oxidase activity. Immunohistochemical analysis revealed that the endothelial expression of ICAM-1 ($3.5{\pm}0.4$) and VCAM-1 ($3.8{\pm}0.3$) in diabetic aorta was significantly higher than those in control aorta ($0.9{\pm}0.5$ and $1.6{\pm}0.3$, respectively), accompanied with the enhanced expression of gp91phox, a membrane subunit of NAD(P)H oixdase. Furthermore, there was a strong positive correlation (r=0.89, P＜0.01 in ICAM-1 and r=0.88, P＜0.01 in VCAM-1) between ICAM-1/VCAM-1 expression and vascular production of superoxide. The present data indicate that the increased production of superoxide via NAD(P)H oxidase may explain the enhanced expression of CAM in diabetic vasculatures.

주제어

#Diabetes   #ICAM-1   #VCAM-1   #E-selectin   #NAD(P)H oxidase  

저자의 다른 논문

참고문헌 (40)

1. Babior BM. NADPH oxidase: an update. Blood 93: 1464-1476, 1999 
2. Blankenberg S, Barbaux S, Tiret L. Adhesion molecules and atherosclerosis. Atherosclerosis 170: 191-203, 2003 
3. Davi G, Ciabattoni G, Consoli A, Mezzetti A, Falco A, Santarone S, Pennese E, Vitacolonna E, Bucciarelli T, Costantini F, Capani F, Patrone C. In vivo formation of 8-iso-prostaglandin F2and platelet activation in diabetes mellitus: effects of improved metabolic control and vitamin E supplementation. Circulation 99: 224-229, 1999 
4. Kim YK, Lee MS, Son SM, Kim IJ, Lee WS, Rhim BY, Hong KW, Kim CD. Vascular NADH oxidase is involved in impaired endothelium-dependent vasodilation in OLETF rats, a model of type 2 diabetes. Diabetes 51: 522-527, 2002b 
5. Ribau JCO, Hadcock SJ, Teoh K, DeReske M. Richardson M. Endothelial adhesion molecule expression is enhanced in the aorta and internal mammary artery of diabetic patients. J Surg Res 85: 225-233, 1999 
6. Ross R. The pathogenesis of atherosclerosis: A perspective for the 1990s. Nature 29: 801-809, 1993 
7. Scalia R, Appel JZ, Lefeer AM. Leukocyte-endothelium interaction during the early stages of hypercholesterolemia in the rabbit. Arterioscler Thromb Vasc Biol 18: 1093-1100, 1998 
8. Vasquez-Vivar J, Kalyanaraman B, Martasek P. Superoxide generation by endothelial nitric oxide synthase: the influence of cofactors. Proc Natl Acad Sci USA 95: 9220-9225, 1998 
9. Wagner OF, Jilma B. Putative role of adhesion molecules in metabolic disorders. Horm Metab Res 29: 627-630, 1997 
10. White CR, Darley-Usmar V, Berrington WR. Circulating plasma xanthine oxidase contributes to vascular dysfunction in hypercholesterolemic rabbits. Proc Natl Acad Sci USA 93: 8745-8749, 1996 
11. Zalba G, Beaumont FJ, San Jose G, Fortuno MA, Etayo JC, Diez J. Vascular NADH/NADPH oxidase is involved in enhanced superoxide production in spontaneously hypertensive rats. Hypertension 35: 1055-1061, 2000 
12. Jude EB, Douglas JT, Anderson SG, Young MJ, Boulton AJM. Circulating cellular adhesion molecules ICAM-1, VCAM-1, Pand E-selectin in the prediction of cardiovascular disease in diabetes mellitus. Eur J Intern Med 13: 185-189, 2002 
13. Kim DE, Suh YS, Lee MS, Kim KY, Lee JH, Lee HS, Hong KW, Kim CD. Vascular NAD(P)H oxidase triggers delayed cerebral vasospasm after subarachnoid hemorrhage in rats. Stroke 33: 2687-2691, 2002a 
14. Matsumoto K, Sere Y, Ueki Y, Inukai G, Niiro E, Miyake S. Comparison of serum concentrations of soluble adhesion molecules in diabetic microangiopathy and macroangiopathy. Diabet Med 19: 822-826, 2002 
15. Garber AJ. Effective treatment of hypertension in patients with diabetes mellitus. Clin Cardiol 15: 715-719, 1992 
16. Schmidt KN, Amstad P, Cerutti P, Baeuerle PA. The roles of hydrogen peroxide and superoxide as messengers in the activation of transcription factor NF-kappa B. Chem Biol 2: 13-22, 1995 
17. Zhang L, Zalewski A, Liu Y, Mazurek T, Cowan S, Martin JL, Hofmann SM, Vlassara H, Shi Y. Diabetes-induced oxidative stress and low-grade inflammation in porcine coronary arteries. Circulation 108: 472-478, 2003 
18. Collins T, Read MA, Neish AS, Whitley MZ, Thanos D, Maniatis T. Transcriptional regulation of endothelial cell adhesion molecules: NF-B and cytokine inducible enhancers. FASEB J 9: 899-909, 1995 
19. Sakai A, Kume N, Nishi E, Tanoue K, Miyasaka M, Kita T. P-selectin and vascular cell adhesion molecule-1 are focally expressed in aortas of hypercholesterolemic rabbits before intimal accumulation of macrophages and T lymphocytes. Arterioscler Thromb Vasc Biol 17: 310-316, 1997 
20. Cominacini L, Garbin U, Pasini AF, Paulon T, Davoli A, Campagnola M, Marchi E, Pastorino AM, Gaviraghi G, Lo Cascio V. Lacidipine inhibits the activation of the transcription factor NF-kappa B and the expression of adhesion molecules induced by pro-oxidant signals on endothelial cells. J Hypertens 15: 1633-1640, 1997 
21. Iiyama K, Hajra L, Iiyama M, Li H, DiChiara M, Medoff BD, Cybulsky MI. Patterns of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 expression in rabbit and mouse atherosclerotic lesions and at sites predisposed to lesion formation. Circ Res 85: 199-207, 1999 
22. Fruebis J, Gonzalez V, Silvestre M, Palinski W. Effect of probucol treatment on gene expression of VCAM-1, MCP-1, and M-CSF in the aortic wall of LDL receptor-deficient rabbits during early atherogenesis. Arterioscler Thromb Vasc Biol 17: 1289-1302, 1997 
23. Ghosh S, May MJ, Kopp EB. NF-kappa B and Rel proteins: Evolutionarily conserved mediators of immune responses. Annu Rev Immunol 16: 225-260, 1998 
24. Schmidt A, Crandall J, Hori O, Cao R, Lakatta E. Elevated plasma levels of vascular cell adhesion molecule-1 (VCAM-1) in diabetic patients with microalbuminaria: A marker of vascular dysfunction and progressive vascular disease. Br J Haematol 92: 747-750, 1996 
25. Miller FJ Jr, Gutterman DD, Rios CD, Heistad DD, Davidson BL. Superoxide production in vascular smooth muscle contributes to oxidative stress and impaired relaxation in atherosclerosis. Circ Res 82: 1298-1305, 1998 
26. Hadcock S, Richardson M, Winocour PD, Hatton MWC. Intimal alterations in rabbit aortas during the first 6 months of alloxan-induced diabetes. Arterioscler Thromb 11: 517-529, 1991 
27. Haffner SM, Greenberg AS, Weston WM. Effect of rosiglitazone treatment on nontraditional markers of cardiovascular disease in patients with type 2 diabetes. Circulation 106: 679-684, 2002 
28. Kojda G, Harrison D. Interactions between NO and reactive oxygen species: pathophysiological importance in atherosclerosis, hypertension, diabetes and heart failure. Cardiovasc Res 43: 562-571, 1999 
29. McLeod DS, Lefer DJ, Merges C, Lutty GA. Enhanced expression of intracellular adhesion molecule-1 and P-selectin in the diabetic human retina and choroids. Am J Pathol 147: 642-653, 1995 
30. Chanock SJ, Benna JL, Smith RM, Babior BM. The respiratory burst oxidase. J Biol Chem 269: 24519-24522, 1994 
31. Levin ME, Sicard GA. Peripheral vascular disease in the person with diabetes. In: Rifkin H, Porte D Jr ed, Diabetes Mellitus: Theory and Practice. Elsevier Science, New York, p 768-791, 1990 
32. Parkos CA, Dinauer MC, Walker LE, Allen RA, Jesaitis AJ, Orkin SH. Primary structure and unique expression of the 22-kilodalton light chain of human neutrophil cytochrome b. Proc Natl Acad Sci USA 85: 3319-3323, 1988 
33. Warnholtz A, Nickenig G, Schulz G. Increased NADH oxidasemediated superoxide production in the early stages of atherosclerosis: evidence for involvement of the renin-angiotensin system. Circulation 99: 2027-2033, 1999 
34. Ushio-Fukai M, Zafari AM, Fukui T, Ishizaka N, Griendling KK. p22phox is a critical component of the superoxide-generating NADH/NADPH oxidase system and regulates angiotensin II-induced hypertrophy in vascular smooth muscle cells. J Biol Chem 271: 23317-23321, 1996 
35. Cominacini L, Fratta A, Garbin U, Davoli A, De Santis A, Campagnola M, Rigoni A, Zenti MG, Moghetti P, Lo Cascio V. Elevated levels of soluble E-selectin in patients with IDDM and NIDDM:Relation to metabolic control. Diabetologia 38: 1122-1124, 1995 
36. Jager A, Hinsbergh V, Kostense PJ, Emeis J, Nijpels G, Dekker J. Increased levels of soluble vascular cell adhesion molecule-1 are associated with risk of cardiovascular mortality in type 2 diabetes. Diabetes 49: 485-491, 2000 
37. Haller H. Schaper D, Ziegler W, Philipp S, Kuhlmann M, Distler A, Luft FC. Low-density lipoprotein induces vascular adhesion molecule expression on human endothelial cells. Hypertension 25: 511-516, 1995 
38. Osborn L. Leukocyte adhesion to endothelium in inflammation. Cell 62: 3-6, 1990 
39. Thrasher AJ, Keep NH, Wientjes F, Segal AW. Chronic granulomatous disease. Biochim Biophys Acta 1227: 1-24, 1994 
40. Hwang SJ, Ballantyne CM, Sharret AR, Smith LC, Davis CE, Gotto AM, Boerwinkle E. Circulating adhesion molecules VCAM-1, ICAM-1, and E-selectinin carotid atherosclerosis and incident coronary heart disease cases. Circulation 96: 4219-4225, 1997 

이 논문을 인용한 문헌 (0)

1. 이 논문을 인용한 문헌 없음