Effects of sarpogrelate hydrochloride on adenosine diphosphate- or collagen-induced platelet responses in arteriosclerosis obliterans

Abstract

To evaluate the effects of the 5-HT2 receptor antagonist sarpogrelate hydrochloride (sarpogrelate) on platelet responses in arteriosclerosis obliterans (ASO), we examined platelet aggregation and its relationships to platelet-derived growth factor (PDGF), soluble P-selectin (sP-selectin), and transforming growth factor-beta 1 (TGF-beta1). Circulating plasma levels of PDGF and sP-selectin in 13 patients with ASO after 1 week of medication with sarpogrelate were significantly lower than those before medication. In contrast, circulating plasma levels of TGF-beta1 after medication were significantly higher than those before medication. When platelet-rich plasma obtained from ASO patients after medication was stimulated with adenosine diphosphate (ADP) or collagen, platelet aggregation was suppressed compared with rates before medication. Significant decreases in levels of PDGF, sP-selectin and TGF-beta1 released from platelets in response to 5 micromol/l ADP and 1 microg/ml collagen after taking of sarpogrelate were found. There were close correlations between platelet aggregation and respective molecules released from platelets. In conclusion, since platelet activation is involved in pathogenesis of thrombotic disease, sarpogrelate may suppress the development of obstructive arteriosclerosis. PDGF and TGF-beta1, as well as sP-selectin, appear to be useful markers for clinical evaluation of anti-platelet drugs.