Masato Kajikawa1, Tatsuya Maruhashi2, Yumiko Iwamoto2, Akimichi Iwamoto2, Nozomu Oda2, Shinji Kishimoto2, Shogo Matsui2, Yoshiki Aibara3, Takayuki Hidaka2, Yasuki Kihara2, Kazuaki Chayama4, Chikara Goto5, Kensuke Noma6, Ayumu Nakashima3, Takanori Matsui7, Sho-Ichi Yamagishi7, Yukihito Higashi8. 1. Division of Regeneration and Medicine, Medical Center for Translational and Clinical Research, Hiroshima University Hospital, Hiroshima, Japan. 2. Department of Cardiovascular Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan. 3. Department of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan. 4. Department of Gastroenterology and Metabolism, Institute of Biomedical and Health Sciences, Graduate School of Biomedical and Health Sciences, Hiroshima University Hiroshima, Japan. 5. Hiroshima International University, Hiroshima, Japan. 6. Division of Regeneration and Medicine, Medical Center for Translational and Clinical Research, Hiroshima University Hospital, Hiroshima, Japan; Department of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan. 7. Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan. 8. Division of Regeneration and Medicine, Medical Center for Translational and Clinical Research, Hiroshima University Hospital, Hiroshima, Japan; Department of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan. Electronic address: yhigashi@hiroshima-u.ac.jp.
Abstract
BACKGROUND: Pigment epithelium-derived factor (PEDF) is a glycoprotein that belongs to the superfamily of serine protease inhibitors. It is thought that PEDF plays a protective role against atherosclerosis. Clinical studies have shown that serum levels of PEDF are increased in subjects with cardiovascular risk factors. The role of PEDF in cardiovascular disease is still controversial. The purpose of this study was to evaluate the associations between serum levels of PEDF and vascular function and structure. METHODS: We measured serum levels of PEDF, assessed vascular function by measurements of flow-mediated vasodilation (FMD) and nitroglycerine-induced vasodilation in the brachial artery, and measured brachial artery intima-media thickness (IMT) in 150 subjects who underwent health examinations. RESULTS AND CONCLUSIONS: Univariate regression analysis revealed that serum level of PEDF was significantly correlated with body mass index, high-density lipoprotein cholesterol, glucose, FMD, nitroglycerine-induced vasodilation, and brachial artery IMT. Multivariate analysis revealed that serum levels of PEDF remained an independent predictor of nitroglycerine-induced vasodilation (β=-0.20, P=0.02) and brachial artery IMT (β=0.14, P=0.03) after adjustment of cardiovascular risk factors, while serum level of PEDF was not associated with FMD (β=-0.02, P=0.79). These findings suggest that PEDF may be a factor directly associated with atherosclerosis. The serum level of PEDF may be a new biochemical marker of atherosclerosis.
BACKGROUND:Pigment epithelium-derived factor (PEDF) is a glycoprotein that belongs to the superfamily of serine protease inhibitors. It is thought that PEDF plays a protective role against atherosclerosis. Clinical studies have shown that serum levels of PEDF are increased in subjects with cardiovascular risk factors. The role of PEDF in cardiovascular disease is still controversial. The purpose of this study was to evaluate the associations between serum levels of PEDF and vascular function and structure. METHODS: We measured serum levels of PEDF, assessed vascular function by measurements of flow-mediated vasodilation (FMD) and nitroglycerine-induced vasodilation in the brachial artery, and measured brachial artery intima-media thickness (IMT) in 150 subjects who underwent health examinations. RESULTS AND CONCLUSIONS: Univariate regression analysis revealed that serum level of PEDF was significantly correlated with body mass index, high-density lipoprotein cholesterol, glucose, FMD, nitroglycerine-induced vasodilation, and brachial artery IMT. Multivariate analysis revealed that serum levels of PEDF remained an independent predictor of nitroglycerine-induced vasodilation (β=-0.20, P=0.02) and brachial artery IMT (β=0.14, P=0.03) after adjustment of cardiovascular risk factors, while serum level of PEDF was not associated with FMD (β=-0.02, P=0.79). These findings suggest that PEDF may be a factor directly associated with atherosclerosis. The serum level of PEDF may be a new biochemical marker of atherosclerosis.