Increased CD40 ligand and platelet-monocyte aggregates in patients with type 1 diabetes mellitus

被引:92
作者
Harding, SA
Sommerfield, AJ
Sarma, J
Twomey, PJ
Newby, DE
Frier, BM
Fox, KAA
机构
[1] Univ Edinburgh, Royal Infirm Edinburgh, Cardiovasc Res Unit, Edinburgh EH3 9YW, Midlothian, Scotland
[2] Univ Edinburgh, Royal Infirm Edinburgh, Dept Diabet, Edinburgh EH3 9YW, Midlothian, Scotland
[3] Univ Edinburgh, Royal Infirm Edinburgh, Dept Clin Biochem, Edinburgh EH3 9YW, Midlothian, Scotland
关键词
diabetes mellitus; inflammation; atherosclerosis; platelets; leukocytes;
D O I
10.1016/j.atherosclerosis.2004.05.008
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background: Diabetes mellitus is a major risk factor for cardiovascular disease and is associated with a proinflammatory and prothrombotic state. We investigated whether CD40 ligand (L) expression and platelet-monocyte aggregation are increased in patients with type 1 diabetes. Methods: Serum C-reactive protein (CRP) and soluble (s) CD40L concentrations, platelet surface CD40L expression and platelet-monocyte aggregates were measured in 22 patients with uncomplicated type 1 diabetes and 22 age- and sex-matched non-diabetic control subjects. Results: In comparison to controls, patients with type 1 diabetes had higher serum CRP concentrations (3.29 +/- 0.9 mg/L versus 0.99 +/- 0.2 mg/L, P = 0.01), serum sCD40L concentrations (10.0 +/- 1.4 ng/mL versus 4.6 +/- 0.6 ng/mL, P = 0.006), and platelet surface expression of CD40L (13.8 +/- 0.9% versus 8.5 +/- 1.1%, P < 0.001). Platelet-monocyte aggregates were also significantly elevated in type 1 diabetes (35.9 +/- 3.3% versus 26.4 +/- 2.9%, P 0.005; n = 10). We also observed a significant correlation between plasma glucose and serum CRP (r = 0.53, P = 0.01) as well as platelet-monocyte aggregates (r = 0.69, P = 0.03). Conclusions: Type 1 diabetes is associated with increased CD40L expression and platelet-monocyte aggregation, which may contribute to the proinflammatory and prothrombotic state as well as the accelerated atherogenesis associated with this disorder. (C) 2004 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:321 / 325
页数:5
相关论文
共 28 条
[1]   Insulin inhibits NFκB and MCP-1 expression in human aortic endothelial cells [J].
Aljada, A ;
Ghanim, H ;
Saadeh, R ;
Dandona, P .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2001, 86 (01) :450-453
[2]   CD40L stabilizes arterial thrombi by a β3 integrin-dependent mechanism [J].
André, P ;
Prasad, KSS ;
Denis, CV ;
He, M ;
Papalia, JM ;
Hynes, RO ;
Phillips, DR ;
Wagner, DD .
NATURE MEDICINE, 2002, 8 (03) :247-252
[3]   Enhanced levels of soluble and membrane-bound CD40 ligand in patients with unstable angina -: Possible reflection of T lymphocyte and platelet involvement in the pathogenesis of acute coronary syndromes [J].
Aukrust, P ;
Müller, F ;
Ueland, T ;
Berget, T ;
Aaser, E ;
Brunsvig, A ;
Solum, NO ;
Forfang, K ;
Froland, SS ;
Gullestad, L .
CIRCULATION, 1999, 100 (06) :614-620
[4]   P-SELECTIN INDUCES THE EXPRESSION OF TISSUE FACTOR ON MONOCYTES [J].
CELI, A ;
PELLEGRINI, G ;
LORENZET, R ;
DEBLASI, A ;
READY, N ;
FURIE, BC ;
FURIE, B .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (19) :8767-8771
[5]   Anti-inflammatory and profibrinolytic effect of insulin in acute ST-segment-elevation myocardial infarction [J].
Chaudhuri, A ;
Janicke, D ;
Wilson, MF ;
Tripathy, D ;
Garg, R ;
Bandyopadhyay, A ;
Calieri, J ;
Hoffmeyer, D ;
Syed, T ;
Ghanim, H ;
Aljada, A ;
Dandona, P .
CIRCULATION, 2004, 109 (07) :849-854
[6]   Insulin inhibits intranuclear nuclear factor κB and stimulates IκB in mononuclear cells in obese subjects:: Evidence for an anti-inflammatory effect? [J].
Dandona, P ;
Aljada, A ;
Mohanty, P ;
Ghanim, H ;
Hamouda, W ;
Assian, E ;
Ahmad, S .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2001, 86 (07) :3257-3265
[7]   Inflammatory cytokine concentrations are acutely increased by hyperglycemia in humans - Role of oxidative stress [J].
Esposito, K ;
Nappo, F ;
Marfella, R ;
Giugliano, G ;
Giugliano, F ;
Ciotola, M ;
Quagliaro, L ;
Ceriello, A ;
Giugliano, D .
CIRCULATION, 2002, 106 (16) :2067-2072
[8]   Soluble CD40 ligand in acute coronary syndromes [J].
Heeschen, C ;
Dimmeler, S ;
Hamm, CW ;
van den Brand, MJ ;
Boersma, E ;
Zeiher, AM ;
Simoons, ML ;
CAPTURE Study Investigators .
NEW ENGLAND JOURNAL OF MEDICINE, 2003, 348 (12) :1104-1111
[9]   CD40 ligand on activated platelets triggers an inflammatory reaction of endothelial cells [J].
Henn, V ;
Slupsky, JR ;
Gräfe, M ;
Anagnostopoulos, I ;
Förster, R ;
Müller-Berghaus, G ;
Kroczek, RA .
NATURE, 1998, 391 (6667) :591-594
[10]   EXPRESSION OF FUNCTIONAL CD40 BY VASCULAR ENDOTHELIAL-CELLS [J].
HOLLENBAUGH, D ;
MISCHELPETTY, N ;
EDWARDS, CP ;
SIMON, JC ;
DENFELD, RW ;
KEINER, PA ;
ARUFFO, A .
JOURNAL OF EXPERIMENTAL MEDICINE, 1995, 182 (01) :33-40