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Letters to the Editor |
1 Suiyukai Clinic, Kashihara, Japan
2 Department of Internal Medicine, Kurume University School of Medicine, Kurume, Japan
3 Cytokine Section, SRL Inc, Kanagawa, Japan
aAddress correspondence to this author at: Department of Internal Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan. Fax 81-942-317707; e-mail shoichi{at}med.kurume-u.ac.jp.
To the Editor:
Pigment epithelium-derived factor (PEDF), a glycoprotein that belongs to the superfamily of serine protease inhibitors, was first purified from the conditioned media of human retinal pigment epithelial cells; it possesses potent neuronal differentiating activity (1). Recently, PEDF has been shown to be a highly effective inhibitor of angiogenesis. In cell culture and in animal models, PEDF inhibited endothelial cell (EC) growth and migration and suppressed ischemia-induced neovascularization (1). In addition, PEDF was reported to inhibit tumor necrosis factor-
-induced or angiotensin II-induced EC activation via its antioxidative properties (2). These observations suggest that PEDF may play a protective role against atherosclerosis by suppressing proliferative inflammatory responses to injuries in ECs. Therefore, characterization of the generation and clearance of PEDF could elucidate the pathophysiological role of this multifunctional protein in vivo.
In a recent study of a general population of Japanese residents [mean (SD) age 65.7 (9.3) years; 71 men and 125 women] who showed no clinical evidence of coronary or peripheral arterial occlusive diseases, we found that serum PEDF concentrations showed a distribution, within the reference interval, of 8 to 24 mg/L [mean (SD) 14.6 (3.2) mg/L], and 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 concentrations (3). In a previous study, we also showed that age- and uric acid-adjusted PEDF concentrations were substantially higher in proportion to the accumulation of components of the metabolic syndrome. Furthermore, the expression of PEDF in porcine liver has been associated with body muscularity and obesity (3). In addition, the concentration of PEDF is down-regulated during the differentiation process of preadipocytes to mature adipocytes (3). These observations suggest that serum PEDF concentrations may increase as a counter-system against coronary risk factors in the metabolic syndrome and that liver and/or adipocytes may be a main source of PEDF in the circulation. However, the clearance of PEDF is not yet characterized, and we do not yet know the relation of serum PEDF concentrations to renal function. Therefore, in this study, we used an ELISA system to investigate whether serum concentrations of PEDF increased in patients with end-stage renal disease (ESRD).
The study protocol was approved by our institutional ethics committee, and informed consent was obtained from study participants. We tested 50 patients [mean (SD) age, 60.5 (10.7) years] with clinical manifestations of ESRD—46 were diagnosed with chronic glomerulonephritis and 4 with polycystic kidney. We also selected 50 healthy control participants, at random, by frequency matching age and sex from 184 residents of a nearby community (62 men and 122 women) who had received health examinations in 2004. Blood was drawn from the antecubital vein in the morning to determine PEDF and blood chemistries. PEDF concentrations were determined with ELISA (3). Inter- (n = 17) and intraassay (n = 14) CVs of the ELISA were 4.7% and 7.3%, respectively. Mean (SD) recovery of the added recombinant PEDF in serum samples was 94.2 (1.7)%. The assay linearity was intact with serial dilution of serum. With Western blot analysis we also confirmed the specific interaction between the PEDF antibody used for the ELISA and PEDF in the samples (3). Other blood chemistries in Table 1
were determined enzymatically at a commercial laboratory (SRL Inc.). Ankle-brachial index and carotid intima-media thickness were measured according to the method of Hayashi et al. (4).
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Characteristics of the patients with ESRD and the control participants are presented in Table 1
. Total cholesterol, LDL-cholesterol, blood urea nitrogen (BUN), creatinine, and uric acid were markedly higher in patients with ESRD than in age- and sex-matched controls, whereas ABI, HDL-cholesterol, total protein, albumin, aspartate aminotransferase, and alanine aminotransferase were markedly lower in ESRD patients. Furthermore, serum PEDF concentrations were markedly higher in ESRD patients than in controls [36.3 (5.7) vs 14.5 (2.3) mg/L, P <0.001] (Table 1
). Univariate analysis revealed that conditions statistically and significantly related to PEDF concentrations were age (P = 0.04, inversely), BUN (P = 0.005), and creatinine (P = 0.006). Because these significant conditions were closely correlated with each other, we performed multiple linear regression analyses. We found that BUN was the sole independent determinant of PEDF (P = 0.02, R2 = 0.295).
In our study, we demonstrated that serum PEDF concentrations were substantially higher in ESRD patients than in controls and that BUN was the sole independent determinant of PEDF.
References
The following articles in journals at HighWire Press have cited this article:
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  Y. Yoshida, S.-i. Yamagishi, T. Matsui, K. Nakamura, T. Imaizumi, K. Yoshimura, and R. Yamakawa Positive correlation of pigment epithelium-derived factor and total antioxidant capacity in aqueous humour of patients with uveitis and proliferative diabetic retinopathy Br J Ophthalmol, September 1, 2007; 91(9): 1133 - 1134. [Abstract] [Full Text] [PDF]
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 N. Ogata, M. Matsuoka, K. Matsuyama, C. Shima, A. Tajika, T. Nishiyama, M. Wada, N. Jo, A. Higuchi, K. Minamino, et al. Plasma Concentration of Pigment Epithelium-Derived Factor in Patients with Diabetic Retinopathy J. Clin. Endocrinol. Metab., March 1, 2007; 92(3): 1176 - 1179. [Abstract] [Full Text] [PDF]
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