Department of Medicine and Molecular Sciences, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
Clin Biochem. 2012 Dec;45(18):1554-7. doi: 10.1016/j.clinbiochem.2012.07.106. Epub 2012 Aug 3.
Pigment epithelium-derived factor (PEDF) is a glycoprotein that belongs to the superfamily of serine protease inhibitors with complex anti-oxidative, anti-fibrotic, and anti-inflammatory properties, thus being involved in cardiometabolic disorders. Nonalcoholic fatty liver disease (NAFLD) is a hepatic manifestation of the metabolic syndrome as well. However, the pathophysiological role of PEDF in NAFLD remains largely unknown. We studied here the relationship between serum PEDF levels and various clinical markers of NAFLD in humans.
The study involved 194 biopsy-proven NAFLD patients (102 male and 92 female) with a mean age of 51.3±13.8 years. We examined which anthropometric, metabolic and inflammatory variables, and liver steatosis and fibrosis markers are independently associated with serum levels of PEDF.
Mean serum levels of PEDF were 16.4±5.7 μg/mL. Univariate analysis revealed that age (inversely), male, body mass index, waist circumference, numbers of white blood cells and platelets, aspartate aminotransferase, alanine aminotransferase, fasting plasma glucose, glycated hemoglobin, uric acid, procollagen type III N-terminal peptide (P-III-P), subcutaneous fat areas, visceral fat areas and liver to spleen density ratio in computed tomography, the presence of diabetes and medication for hyperlipidemia were significantly associated with serum levels of PEDF. In multiple stepwise regression analysis, age (p<0.01, inversely), male (p<0.05), waist circumference (p<0.01), white blood cell number (p<0.05), P-III-P (p<0.05), and the presence of diabetes (p<0.05) and medication for hyperlipidemia (p<0.01), were independently correlated to serum levels of PEDF (R(2)=0.285).
The present study reveals that serum levels of PEDF are independently associated with P-III-P levels, suggesting that PEDF level is a novel biomarker of liver fibrosis in patients with NAFLD.
色素上皮衍生因子(PEDF)是一种糖蛋白,属于丝氨酸蛋白酶抑制剂超家族,具有复杂的抗氧化、抗纤维化和抗炎特性,因此参与了心脏代谢紊乱。非酒精性脂肪性肝病(NAFLD)也是代谢综合征的肝脏表现。然而,PEDF 在 NAFLD 中的病理生理作用在很大程度上仍然未知。我们在这里研究了血清 PEDF 水平与人类 NAFLD 的各种临床标志物之间的关系。
该研究涉及 194 名经活检证实的 NAFLD 患者(102 名男性和 92 名女性),平均年龄为 51.3±13.8 岁。我们检查了哪些人体测量、代谢和炎症变量以及肝脂肪变性和纤维化标志物与血清 PEDF 水平独立相关。
平均血清 PEDF 水平为 16.4±5.7 μg/mL。单因素分析显示,年龄(负相关)、男性、体重指数、腰围、白细胞和血小板数、天门冬氨酸氨基转移酶、丙氨酸氨基转移酶、空腹血糖、糖化血红蛋白、尿酸、III 型前胶原 N 端肽(P-III-P)、皮下脂肪面积、内脏脂肪面积和计算机断层扫描肝脏与脾脏密度比、糖尿病和高脂血症药物治疗与血清 PEDF 水平显著相关。在多元逐步回归分析中,年龄(p<0.01,负相关)、男性(p<0.05)、腰围(p<0.01)、白细胞数(p<0.05)、P-III-P(p<0.05)、糖尿病(p<0.05)和高脂血症药物治疗(p<0.01)与血清 PEDF 水平独立相关(R(2)=0.285)。
本研究表明,血清 PEDF 水平与 P-III-P 水平独立相关,提示 PEDF 水平是 NAFLD 患者肝纤维化的新型生物标志物。