title: Platelet activation markers, microparticles and soluble adhesion molecules are elevated in patients with arteriosclerosis obliterans: therapeutic effects by cilostazol and potentiation by dipyridamole.
abstract: We evaluated the plasma concentrations of platelet activation markers, microparticles and soluble adhesion molecules in patients with arteriosclerosis obliterans (ASO) and compared the beneficial effects of cilostazol alone and combination therapy of cilostazol and dipyridamole in these patients. There was a significant elevation of CD62P, CD63, PAC-1, annexin V, platelet-derived microparticles (PDMPs), sP-selectin, sE-selectin, sICAM-1 and sVCAM-1 in the ASO patients compared with the controls. Platelet aggregation was decreased by 2 weeks of cilostazol monotherapy in the ASO patients. Adding dipyridamole to the cilostazol therapy for 2 weeks further reduced platelet aggregation. While treatment with cilostazol alone reduced levels of CD62P, CD63, PAC-1, annexin V, PDMP, and sP-selectin, the combination therapy reduced these parameters further. While sE-selectin and cell adhesion molecules did not change significantly after 2 weeks of combination therapy, they exhibited a remarkable decrease after 16 weeks of combination treatment. These findings suggest that platelets are activated in ASO patients, and cilostazol is effective to reduce platelet activation. Furthermore, dipyridamole may potentiate the beneficial effect of cilostazol in ASO patients. Combination use of both drugs may help to prevent the onset of cardiovascular complications in patients with ASO by activated platelets and PDMP.
authors.affiliation: First Department of Internal Medicine, Kansai Medical University, 10-15 Fumizonocho, Moriguchi, Osaka 570-8507, Japan. shosaku-n@mbp.ocn.ne.jp
authors.forename: Shosaku
authors.initials: S
authors.lastname: Nomura
authors.forename: Norihito
authors.initials: N
authors.lastname: Inami
authors.forename: Toshiji
authors.initials: T
authors.lastname: Iwasaka
authors.forename: Yongge
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000368:Aged; D001162:Arteriosclerosis Obliterans / Q000097:blood* / Q000188:drug therapy*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules / Q000097:blood; D000077407:Cilostazol; D004176:Dipyridamole / Q000008:administration & dosage* / Q000494:pharmacology; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010316:Particle Size; D015539:Platelet Activation / Q000187:drug effects*; D013777:Tetrazoles / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D015415:Biomarkers; D015815:Cell Adhesion Molecules; D013777:Tetrazoles; D004176:Dipyridamole; D000077407:Cilostazol