EFFECT OF CILOSTAZOL ON SOLUBLE ADHESION MOLECULES AND PLATELET-DERIVED MICROPARTICLES IN PATIENTS WITH DIABETES

We evaluated the plasma concentrations of soluble adhesion molecules a nd platelet-derived microparticles (PMP) in patients with noninsulin d ependent diabetes mellitus (NIDDM) and studied the effect of cilostazo l on PMP generation. There were differences in the levels of soluble a dhesion molecules between NIDDM patients (N = 43) and the control subj ects (N = 30) (soluble thrombomodulin: 11.5 +/- 5.3 vs. 7.0 +/- 1.2 TU /ml, p<0.0001; soluble vascular cell adhesion molecule-1: 708 +/- 203 vs. 492 +/- 113 ng/dl p<0.0001; soluble intercellular cell adhesion mo lecules-1: 274 +/- 65 vs. 206 +/- 48 ng/dl. p<0.0001; soluble P-select in: 194 +/- 85 vs. 125 +/- 43 ng/dl. p<0.0001). There were also differ ences in the levels of PMP and platelet activation markers between NID DM patients and the controls (PMP: 943 +/-: 504 vs. 488 +/- 219/10(4) pit, p<0.0001: platelet CD62P: 9.2 +/- 4.6 vs. 4.4 +/- 4.3%, p<0.001: platelet CD63: 10.2 +/- 4.5 vs. 4.5 +/- 3.3%, p<0.0001; platelet annex in V: 9.1 +/- 3.9 vs. 5.3 +/- 3.8%, p<0.001). To study the release of PMP into plasma, a modified cone-and-plate viscometer was used. Increa sed release of PMP from platelets was observed in diabetic plasma comp ared to normal plasma under high shear stress conditions (2.672 +/- 64 5 vs. 1.498 +/- 386/10(4) pit, p<0.05). Therefore. one cause of PMP el evation in NIDDM may be high shear stress. The levels of PMP, activate d platelets. and soluble adhesion molecules all decreased significantl y after treatment with cilostazol. These results suggest that cilostaz ol may be useful for the inhibition of both PMP-dependent and -indepen dent vascular damage in NIDDM.