Pigment epithelium-derived factor (PEDF) prevents platelet activation and aggregation in diabetic rats by blocking deleterious effects of advanced glycation end products (AGEs)

Sho Ichi Yamagishi, Takanori Matsui, Katsuhiko Takenaka, Kazuo Nakamura, Masayoshi Takeuchi, Hiroyoshi Inoue

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Background: Alteration of platelet function contributes to microthrombus formation and may play an important role in the pathogenesis of diabetic vascular complications. In addition, there is a growing body of evidence that oxidative stress generation is involved in platelet activation and aggregation in vivo. Since we have recently found that pigment epithelium-derived factor (PEDF) inhibits thrombus formation in rats through its anti-oxidative properties, we investigated here whether PEDF prevented platelet activation and aggregation in diabetic or advanced glycation end products (AGEs)-injected rats. Methods and Results: Experimental diabetes was induced by injecting streptozotocin to Sprague-Dawley rats. Diabetic or non-diabetic Sprague-Dawley rats were injected intravenously with or without 1 mg AGEs-bovine serum albumin or non-glycated bovine serum albumin in the presence or absence of 10 μg PEDF everyday. Administration of PEDF or pyridoxal phosphate, an inhibitor of AGEs formation, inhibited platelet P-selectin expression and aggregation by suppressing NADPH oxidase-driven superoxide generation, and subsequently ameliorated a shortened tail vein bleeding time in diabetic rats. Further, intravenous administration of AGEs to normal rats mimicked the effects of diabetes on platelet activation and bleeding time, which were also blocked by simultaneous administration of PEDF. Conclusions: These results demonstrated for the first time that PEDF inhibited platelet activation and aggregation in diabetic rats through its anti-oxidative properties. Our present study suggests that PEDF may play a protective role against diabetic vascular complications by attenuating the deleterious effects of AGEs on platelets.

Original languageEnglish
Pages (from-to)266-271
Number of pages6
JournalDiabetes/Metabolism Research and Reviews
Volume25
Issue number3
DOIs
Publication statusPublished - 2009
Externally publishedYes

Fingerprint

Advanced Glycosylation End Products
Platelet Activation
Platelet Aggregation
Diabetic Angiopathies
Bleeding Time
Blood Platelets
Bovine Serum Albumin
Sprague Dawley Rats
Pyridoxal Phosphate
P-Selectin
NADPH Oxidase
Streptozocin
pigment epithelium-derived factor
Superoxides
Intravenous Administration
Tail
Veins
Oxidative Stress
Thrombosis

Keywords

  • AGEs
  • Diabetes
  • Oxidative stress
  • PEDF
  • Platelets

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Internal Medicine

Cite this

Pigment epithelium-derived factor (PEDF) prevents platelet activation and aggregation in diabetic rats by blocking deleterious effects of advanced glycation end products (AGEs). / Yamagishi, Sho Ichi; Matsui, Takanori; Takenaka, Katsuhiko; Nakamura, Kazuo; Takeuchi, Masayoshi; Inoue, Hiroyoshi.

In: Diabetes/Metabolism Research and Reviews, Vol. 25, No. 3, 2009, p. 266-271.

Research output: Contribution to journalArticle

@article{fdadbe2d2b9b4836984657e097deca62,
title = "Pigment epithelium-derived factor (PEDF) prevents platelet activation and aggregation in diabetic rats by blocking deleterious effects of advanced glycation end products (AGEs)",
abstract = "Background: Alteration of platelet function contributes to microthrombus formation and may play an important role in the pathogenesis of diabetic vascular complications. In addition, there is a growing body of evidence that oxidative stress generation is involved in platelet activation and aggregation in vivo. Since we have recently found that pigment epithelium-derived factor (PEDF) inhibits thrombus formation in rats through its anti-oxidative properties, we investigated here whether PEDF prevented platelet activation and aggregation in diabetic or advanced glycation end products (AGEs)-injected rats. Methods and Results: Experimental diabetes was induced by injecting streptozotocin to Sprague-Dawley rats. Diabetic or non-diabetic Sprague-Dawley rats were injected intravenously with or without 1 mg AGEs-bovine serum albumin or non-glycated bovine serum albumin in the presence or absence of 10 μg PEDF everyday. Administration of PEDF or pyridoxal phosphate, an inhibitor of AGEs formation, inhibited platelet P-selectin expression and aggregation by suppressing NADPH oxidase-driven superoxide generation, and subsequently ameliorated a shortened tail vein bleeding time in diabetic rats. Further, intravenous administration of AGEs to normal rats mimicked the effects of diabetes on platelet activation and bleeding time, which were also blocked by simultaneous administration of PEDF. Conclusions: These results demonstrated for the first time that PEDF inhibited platelet activation and aggregation in diabetic rats through its anti-oxidative properties. Our present study suggests that PEDF may play a protective role against diabetic vascular complications by attenuating the deleterious effects of AGEs on platelets.",
keywords = "AGEs, Diabetes, Oxidative stress, PEDF, Platelets",
author = "Yamagishi, {Sho Ichi} and Takanori Matsui and Katsuhiko Takenaka and Kazuo Nakamura and Masayoshi Takeuchi and Hiroyoshi Inoue",
year = "2009",
doi = "10.1002/dmrr.906",
language = "English",
volume = "25",
pages = "266--271",
journal = "Diabetes/Metabolism Research and Reviews",
issn = "1520-7552",
publisher = "John Wiley and Sons Ltd",
number = "3",

}

TY - JOUR

T1 - Pigment epithelium-derived factor (PEDF) prevents platelet activation and aggregation in diabetic rats by blocking deleterious effects of advanced glycation end products (AGEs)

AU - Yamagishi, Sho Ichi

AU - Matsui, Takanori

AU - Takenaka, Katsuhiko

AU - Nakamura, Kazuo

AU - Takeuchi, Masayoshi

AU - Inoue, Hiroyoshi

PY - 2009

Y1 - 2009

N2 - Background: Alteration of platelet function contributes to microthrombus formation and may play an important role in the pathogenesis of diabetic vascular complications. In addition, there is a growing body of evidence that oxidative stress generation is involved in platelet activation and aggregation in vivo. Since we have recently found that pigment epithelium-derived factor (PEDF) inhibits thrombus formation in rats through its anti-oxidative properties, we investigated here whether PEDF prevented platelet activation and aggregation in diabetic or advanced glycation end products (AGEs)-injected rats. Methods and Results: Experimental diabetes was induced by injecting streptozotocin to Sprague-Dawley rats. Diabetic or non-diabetic Sprague-Dawley rats were injected intravenously with or without 1 mg AGEs-bovine serum albumin or non-glycated bovine serum albumin in the presence or absence of 10 μg PEDF everyday. Administration of PEDF or pyridoxal phosphate, an inhibitor of AGEs formation, inhibited platelet P-selectin expression and aggregation by suppressing NADPH oxidase-driven superoxide generation, and subsequently ameliorated a shortened tail vein bleeding time in diabetic rats. Further, intravenous administration of AGEs to normal rats mimicked the effects of diabetes on platelet activation and bleeding time, which were also blocked by simultaneous administration of PEDF. Conclusions: These results demonstrated for the first time that PEDF inhibited platelet activation and aggregation in diabetic rats through its anti-oxidative properties. Our present study suggests that PEDF may play a protective role against diabetic vascular complications by attenuating the deleterious effects of AGEs on platelets.

AB - Background: Alteration of platelet function contributes to microthrombus formation and may play an important role in the pathogenesis of diabetic vascular complications. In addition, there is a growing body of evidence that oxidative stress generation is involved in platelet activation and aggregation in vivo. Since we have recently found that pigment epithelium-derived factor (PEDF) inhibits thrombus formation in rats through its anti-oxidative properties, we investigated here whether PEDF prevented platelet activation and aggregation in diabetic or advanced glycation end products (AGEs)-injected rats. Methods and Results: Experimental diabetes was induced by injecting streptozotocin to Sprague-Dawley rats. Diabetic or non-diabetic Sprague-Dawley rats were injected intravenously with or without 1 mg AGEs-bovine serum albumin or non-glycated bovine serum albumin in the presence or absence of 10 μg PEDF everyday. Administration of PEDF or pyridoxal phosphate, an inhibitor of AGEs formation, inhibited platelet P-selectin expression and aggregation by suppressing NADPH oxidase-driven superoxide generation, and subsequently ameliorated a shortened tail vein bleeding time in diabetic rats. Further, intravenous administration of AGEs to normal rats mimicked the effects of diabetes on platelet activation and bleeding time, which were also blocked by simultaneous administration of PEDF. Conclusions: These results demonstrated for the first time that PEDF inhibited platelet activation and aggregation in diabetic rats through its anti-oxidative properties. Our present study suggests that PEDF may play a protective role against diabetic vascular complications by attenuating the deleterious effects of AGEs on platelets.

KW - AGEs

KW - Diabetes

KW - Oxidative stress

KW - PEDF

KW - Platelets

UR - http://www.scopus.com/inward/record.url?scp=65649133985&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=65649133985&partnerID=8YFLogxK

U2 - 10.1002/dmrr.906

DO - 10.1002/dmrr.906

M3 - Article

C2 - 19165765

AN - SCOPUS:65649133985

VL - 25

SP - 266

EP - 271

JO - Diabetes/Metabolism Research and Reviews

JF - Diabetes/Metabolism Research and Reviews

SN - 1520-7552

IS - 3

ER -