Increased serum HMGB1 level is associated with coronary artery disease in nondiabetic and type 2 diabetic patients.
OBJECTIVE
This cross-sectional study tested the hypothesis that increased serum level of high mobility group box-1 protein (HMGB1), a pro-inflammatory ligand of receptor for advanced glycation end products (RAGE), is associated with coronary artery disease (CAD) in nondiabetic and type 2 diabetic patients.


METHODS
Serum levels of HMGB1, endogenous secretory RAGE (esRAGE), soluble RAGE (sRAGE) and inflammatory cytokines were determined in 512 patients categorized as Group I (n=132, without diabetes and CAD), Group II (n=149, with CAD but no diabetes), Group III (n=80, with diabetes but no CAD) and Group IV (n=151, with diabetes and CAD).


RESULTS
Serum levels of HMGB1 and hsCRP were higher in Group II than in Group I, and in Group IV than in Group III (all P<0.001). HMGB1 was positively related to hsCRP, TNF-alpha and IL-6 levels in the whole subjects (all P<0.01). Group II patients had lower sRAGE (P=0.058) and esRAGE (P<0.001) levels versus those in Group I. However, in the diabetic patients, those in Group IV had lower esRAGE (P<0.001) but higher sRAGE (P=0.002) levels compared to those in Group III. In multivariable regression analysis, HMGB1, esRAGE and conventional risk factors (age, smoking, hypertension, HDL-C, hsCRP, TNF-alpha) were independent determinants of CAD in nondiabetic patients. Moreover, HMGB1 and esRAGE consistently remained to be independently associated with CAD in diabetic patients, so did other major conventional risk factors.


CONCLUSIONS
This study demonstrates that increased serum HMGB1 level is associated with CAD in nondiabetic and type 2 diabetic patients.
Yan
Xiao Xiang
XX
Department of Cardiology, Rui Jin Hospital, Jiaotong University School of Medicine, Shanghai, People's Republic of China.
Lu
Lin
L
Peng
Wen Hui
WH
Wang
Ling Jie
LJ
Zhang
Qi
Q
Zhang
Rui Yan
RY
Chen
Qiu Jing
QJ
Shen
Wei Feng
WF
D000368:Aged; D017023:Coronary Angiography / Q000379:methods; D003324:Coronary Artery Disease / Q000097:blood* / Q000175:diagnosis; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000378:metabolism; D048909:Diabetes Complications / Q000097:blood / Q000175:diagnosis; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005260:Female; D024243:HMGB1 Protein / Q000097:blood*; D006801:Humans; D007249:Inflammation; D008024:Ligands; D008297:Male; D008875:Middle Aged; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism; D012307:Risk Factors
D016207:Cytokines; D024243:HMGB1 Protein; D008024:Ligands; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic