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Elevated Serum Levels of Pigment Epithelium-Derived Factor in the Metabolic Syndrome

Department of Internal Medicine III (S.Y., H.A., M.E., K.F., A.H., Y.J., K.T., T.M., K.N., T.I.), Kurume University School of Medicine, Kurume 830-0011, Japan; and Cytokine Section (A.A., T.Y.), SRL Inc., Kanagawa 229-1125, Japan

Address all correspondence and requests for reprints to: Dr. Sho-ichi Yamagishi, Department of Internal Medicine III, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan. E-mail: shoichi{at}med.kurume-u.ac.jp.

Context: Pigment epithelium-derived factor (PEDF), a potent inhibitor of angiogenesis with neuronal differentiating activity, inhibits endothelial cell injury in vitro, thus suggesting the involvement of PEDF in atherosclerosis. Therefore, elucidating the relationship between serum levels of PEDF and coronary risk factors could provide a clue to understanding the pathophysiological role of PEDF in vivo.

Objective: We examined whether serum levels of PEDF were associated with risk factors for coronary artery disease.

Design: The study was designed as a cross-sectional study.

Setting: The study was set within the general community.

Patients or Other Participants: A total of 196 general Japanese residents (age 65.7 ± 9.3 yr; 71 males and 125 females) without clinical evidence of coronary or peripheral arterial occlusive diseases were enrolled in this study.

Results: PEDF showed a normal distribution, ranging from 8–24 µg/ml, with a mean of 14.6 ± 3.2 µg/ml. Multivariate analyses revealed that uric acid (P < 0.001), waist circumference (P = 0.009), insulin (P = 0.019), and triglycerides (P = 0.028) were significant independent determinants of serum PEDF levels. Age- and uric acid-adjusted PEDF levels were significantly higher (P = 0.048 for men and P = 0.007 for women) in proportion to the accumulation of the number of the components of the metabolic syndrome.

Conclusions: The present study reveals that serum levels of PEDF are strongly associated with the metabolic syndrome. Our results suggest that serum PEDF levels may be elevated as a counter-system in the metabolic syndrome.

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