Upregulation of CD40--CD40 ligand system in patients with diabetes mellitus.
BACKGROUND
Diabetes is associated with an increased risk of cardiovascular disease and atherosclerosis. Increasing evidence shows that CD40-CD40L interaction plays a crucial role in the pathogenesis of atherosclerosis and coronary artery disease. The purpose of this study was to assess whether CD40 system expressions were disrupted in patients with diabetes.


METHODS
Sixteen normal controls and 72 patients including 20 with type 2 diabetes mellitus (DM), 15 with type 1 DM, 20 with coronary heart disease (CHD) and 17 CHD with coexisting DM were investigated. The expression of CD40 and CD40L on platelet was analyzed by indirect-immunofluorescence flow cytometry and serum-soluble CD40L level was determined by a commercially available ELISA. Serum of AGE was detected by fluorescence spectroscopy.


RESULTS
Type 1 DM, type 2 DM, CHD and CHD Patients with coexisting diabetes showed a significant increase of CD40 (81.8 +/- 11.7, 70.7 +/- 11.6, 68.5 +/- 10.2, 79.9 +/- 11.9 MIF, respectively) and CD40L (18.4 +/- 5.1, 13.9 +/- 4.1, 13.5 +/- 3.7, 16.7 +/- 4.7 MIF, respectively) coexpression on platelets as well as sCD40L (15.6 +/- 3.5, 14.1 +/- 3.3, 12.2 +/- 3.5, 13.5 +/- 3.6 ng/ml, respectively) compared with controls (p < 0.01). A positive correlation was found between serum AGE levels in patients with DM and CD40-CD40L system. We also observed a significant correlation between hemoglobinA1c (HbA1c) concentration and CD40L on platelets (r = 0.71, p < 0.001) as well as sCD40L (r = 0.69, p < 0.001), but not for CD40 on platelets.


CONCLUSIONS
Patients with diabetes show increased coexpression of CD40 system, especially CD40L, which may create a proinflammatory and prothrombotic milieu for aggravating the development of atherosclerosis.
Jinchuan
Yan
Y
Department of Cardiology, Affiliated Zhong Da Hospital, Southeast University Nanjing 210009, China. yanjinchuan@hotmail.com
Zonggui
Wu
W
Jinming
Chen
C
Li
Li
L
Xiantao
Kong
K
D001786:Blood Glucose / Q000032:analysis; D001792:Blood Platelets / Q000378:metabolism; D019013:CD40 Antigens / Q000097:blood* / Q000378:metabolism; D023201:CD40 Ligand / Q000097:blood* / Q000378:metabolism; D003920:Diabetes Mellitus / Q000097:blood* / Q000378:metabolism; D006441:Hemoglobin A / Q000032:analysis; D006801:Humans; D008875:Middle Aged; D012995:Solubility
D001786:Blood Glucose; D019013:CD40 Antigens; D023201:CD40 Ligand; D006441:Hemoglobin A