Horm Metab Res 2007; 39(11): 845-848
DOI: 10.1055/s-2007-991176
Humans, Clinical

© Georg Thieme Verlag KG Stuttgart · New York

Serum Level of Advanced Glycation End-Products (AGEs) is an Independent Determinant of Plasminogen Activator Inhibitor-1 (PAI-1) in Nondiabetic General Population

S. Yamagishi 1 , H. Adachi 1 , M. Takeuchi 2 , M. Enomoto 1 , K. Furuki 1 , T. Matsui 1 , K. Nakamura 1 , T. Imaizumi 1
  • 1Department of Medicine, Division of Cardiovascular Medicine, Kurume University School of Medicine, Kurume, Japan
  • 2Department of Pathophysiological Science, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan
Further Information

Publication History

received 20.11.2006

accepted 11.04.2007

Publication Date:
09 November 2007 (online)

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Abstract

Glucose can react nonenzymatically with amino groups of proteins to form senescent macroprotein derivatives termed advanced glycation end-products (AGEs). Recently, AGEs have been shown to play an important role in atherosclerosis even in nondiabetic subjects. However, the molecular mechanism underlying this is not fully understood. We have now investigated whether serum AGE level was an independent determinant of plasminogen activator inhibitor-1 (PAI-1), a major physiological inhibitor of fibrinolysis, in nondiabetic general population. One-hundred and eighty-six nondiabetic Japanese subjects underwent a complete history and physical examination, determination of blood chemistries, PAI-1, and AGEs. Uni- and multivariate analyses were applied for the determinants of PAI-1 levels. The average PAI-1 levels were 29.7±23.8 ng/ml in males and 21.8±17.1 ng/ml in females, respectively. Univariate regression analysis showed that PAI-1 levels were associated with age (inversely, p=0.003), male (p=0.003), body mass index (BMI) (p<0.001), HDL-cholesterol (inversely, p<0.001), triglycerides (p<0.001), fasting plasma glucose (p<0.001), insulin (p<0.001), uric acids (p<0.001), AGEs (p=0.037), and alcohol intake (p<0.001). By the use of multiple regression analyses, BMI (p<0.001), male (p=0.003), fasting plasma glucose (p=0.005), age (inversely, p=0.017), and AGEs (p=0.034) remained significant. The present study is the first demonstration that serum AGE level was one of the independent determinants of PAI-1 in nondiabetic general population. The AGE-associated thrombogenic abnormality may be involved in atherogenesis in nondiabetic subjects.

References

Correspondence

S. YamagishiMD, PhD 

Department of Medicine

Division of Cardiovascular Medicine

Kurume University School of Medicine

67 Asahi-machi

830-0011 Kurume

Japan

Email: shoichi@med.kurume-u.ac.jp