Pigment epithelium-derived factor (PEDF) administration inhibits occlusive thrombus formation in rats: a possible participation of reduced intraplatelet PEDF in thrombosis of acute coronary syndromes.
OBJECTIVE
Although remarkable therapeutic advances in the treatment of acute coronary syndromes (ACS) have been made with anti-platelet therapy, the therapeutic options may be limited by considerable side effects. Pigment epithelium-derived factor (PEDF) has anti-oxidative properties and may play a protective role against atherosclerosis. In this study, we investigated whether PEDF prevented occlusive thrombus formation in rats.


RESULTS
Occlusive thrombus formation was induced by treating rats with ligation and cuff placement at the left common carotid artery. Intravenous injection of PEDF dose-dependently inhibited thrombus formation and blocked the increase in immunoreactivity of P-selectin, a marker of platelet activation, NADPH oxidase activity and superoxide generation in thrombi. In vitro, PEDF significantly decreased collagen-induced reactive oxygen species generation in platelets and subsequently suppressed the platelet activation and aggregation. Plasma and intraplatelet levels of PEDF in the coronary circulation in patients with ACS were significantly lower than those in age- and gender-matched controls without coronary artery disease.


CONCLUSIONS
These results demonstrated that PEDF administration could inhibit occlusive thrombus formation by blocking the platelet activation and aggregation through its anti-oxidative properties. Our present study suggests that pharmacological up-regulation or substitution of PEDF may offer a promising strategy for the treatment of arterial thrombosis.
Takenaka
Katsuhiko
K
Department of Medicine, Division of Cardio-Vascular Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan.
Yamagishi
Sho-ichi
S
Matsui
Takanori
T
Nakamura
Kazuo
K
Jinnouchi
Yuko
Y
Yoshida
Yumiko
Y
Ueda
Shin-ichiro
S
Katsuki
Yoshio
Y
Katsuda
Yousuke
Y
Imaizumi
Tsutomu
T
D054058:Acute Coronary Syndrome / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D001157:Arterial Occlusive Diseases / Q000188:drug therapy* / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D002341:Carotid Artery Thrombosis / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005136:Eye Proteins / Q000378:metabolism* / Q000494:pharmacology*; D006801:Humans; D019255:NADPH Oxidases / Q000378:metabolism; D009414:Nerve Growth Factors / Q000378:metabolism* / Q000494:pharmacology*; D019007:P-Selectin / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D015843:Serpins / Q000378:metabolism* / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism; D000099174:Pigment Epithelium-Derived Factor
D005136:Eye Proteins; D019255:NADPH Oxidases; D009414:Nerve Growth Factors; D019007:P-Selectin; D017382:Reactive Oxygen Species; D015843:Serpins; D013481:Superoxides; D000099174:Pigment Epithelium-Derived Factor