Pigment epithelium-derived factor (PEDF) inhibits diabetes- or advanced glycation end product (AGE)-induced platelet CD40 ligand overexpression in rats.
The formation and accumulation of advanced glycation end products (AGEs) have been known to progress under hyperglycemic conditions, thereby being involved in accelerated atherosclerosis in diabetes. We have recently found that pigment epithelium-derived factor (PEDF), a glycoprotein with potent neuronal cell differentiating activity, could play a protective role against cardiovascular disease (CVD) by attenuating the deleterious effects of AGEs. Although there is a growing body of evidence that inhibition of platelet CD40 ligand (CD40L) expression may be a novel therapeutic target for preventing CVD, effects of PEDF on platelet CD40L expression remain to be elucidated. In this study, we examined the effects of PEDF administration on platelet CD40L expression in diabetic or AGE-injected non-diabetic rats. Further, in order to elucidate the clinical relevance of PEDF administration, we studied whether intraplatelet PEDF levels were decreased in diabetic rats. Platelet CD40L expression levels were increased by about 2-folds in diabetic rats, which were partly blocked by the treatment with PEDF. Further, AGE injection to non-diabetic rats was found to increase platelet CD40L expression levels by about 1.3-folds, whose effects were completely prevented by the treatment with PEDF. Intraplatelet PEDF levels in diabetic rats were significantly decreased, compared with control rats. Our present study suggests that PEDF could inhibit platelet CD40L overexpression in diabetes by blocking the effects of AGEs on platelets. Pharmacological up-regulation or substitution of PEDF may offer a novel promising strategy for preventing CVD in diabetes.
Yamagishi
Sho-ichi
S
Matsui
Takanori
T
Ueda
So
S
Takeuchi
Masayoshi
M
D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D023201:CD40 Ligand / Q000096:biosynthesis*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005136:Eye Proteins / Q000502:physiology*; D017127:Glycation End Products, Advanced / Q000502:physiology*; D009414:Nerve Growth Factors / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015843:Serpins / Q000502:physiology*; D000099174:Pigment Epithelium-Derived Factor
D023201:CD40 Ligand; D005136:Eye Proteins; D017127:Glycation End Products, Advanced; D009414:Nerve Growth Factors; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor