Cyclic AMP: A potent inhibitor of DNA synthesis in cultured arterial endothelial and smooth muscle cells

Summary The effect of dibutyryl cyclic AMP on DNA synthesis was studied in cultured human umbilical endothelial cells and rat aortic smooth muscle cells. Dibutyryl cyclic AMP (2×10^-4mol/l) inhibited DNA synthesis in both arterial cell types when they were grown in medium supplemented with whole serum or with platelet poor serum, but had no effect in the absence of serum. An effect was seen one hour after the addition of the nucleotide, and the threshold concentration was between 2×10^-6 and 2×10^-5mol/l. These results may have relevance to the interaction of platelets and insulin with the arterial wall in the development of atherosclerosis in diabetes.     

Leukocyte and platelet activation in patients with giant cell arteritis and polymyalgia rheumatica: A clue to thromboembolic risks?

Ischemia is a leading causes of morbidity in giant cell arteritis (GCA). We studied circulating platelets and leukocytes in patients with GCA and with polymyalgia rheumatica. Normal healthy donors (>60 a) served as controls. Patients had a significantly greater fraction of platelets expressing P-selectin, of platelet–Nph and platelet–Mo aggregates, and of Nph and Mo expressing tissue factor. These differences were correlated with the percentage of platelets expressing P-selectin and were not influenced by clinical features or by systemic inflammation. Activated circulating leukocytes and platelets could contribute to indolent vessel inflammation and possibly to thromboembolic events in patients with systemic large vessel vasculitis.     

Adjunctive Cilostazol versus High Maintenance Dose of Clopidogrel in Patients with Hyporesponsiveness to Chronic Clopidogrel Therapy

Purpose

Whether addition of cilostazol is superior to increasing dose of clopidogrel in patients with hyporesponsiveness to chronic clopidogrel therapy is unknown.

Materials and Methods

We studied 73 patients with hyporesponsiveness to clopidogrel on standard dual antiplatelet therapy for more than 2 weeks. Clopidogrel hyporesponsiveness was defined as percent inhibition of P2Y12 reaction units (PRU) <30% on VerifyNow P2Y12 assay. Patients were randomly assigned to increased dose of clopidogrel (aspirin 100 mg+clopidogrel 150 mg daily: group A, n=38) or to receiving additional cilostazol (aspirin 100 mg+clopidogrel 75 mg+cilostazol 100 mg bid daily: group B, n=35).

Results

Baseline percent inhibition of PRU and PRU was similar between 2 groups (13.0±10.2% versus 11.8±9.7%, p=0.61, and 286.3±54.7 versus 295.7±53.7, p=0.44, respectively). At follow-up, percent inhibition of PRU was higher and PRU was lower significantly in group B than in group A (38.5±17.9% versus 28.3±16.6%, p=0.02, and 207.3±68.2 versus 241.3±76.7, p=0.050, respectively). Among those still showing hyporesponsiveness to clopidogrel at follow-up (21 patients in group A, 10 patients in group B), 12 patients completed further crossover study. Compared to the baseline, magnitude of change in percent inhibition of PRU and PRU showed an improved tendency after the crossover (from 2.7±8.7% to 15.8±18.4%, p=0.08, and from -18.6±58.0 to -61.9±84.3, p=0.08).

Conclusion

Adjunctive cilostazol improved clopidogrel responsiveness better than the higher maintenance dose of clopidogrel in hyporesponsive patients with chronic clopidogrel therapy.     

The role of protonation and conformational transition of polyamine grafts in platelet retention to polyamine-graft-PHEMA copolymer surfaces

Blood platelet retention on polyamine-graft-poly(2-hydroxyethyl methacrylate) (PHEMA) copolymer (HA) surface was investigated, focusing on pH and ionic strength of the surrounding medium to elucidate the nature of ionic interaction between platelets and HA copolymer surfaces. The conformational transition of polyamine graft chain in response to the protonation degree of amino groups was demonstrated to be an important factor influencing platelet retention on HA surfaces. When the polyamine graft chain exists in an extended conformation, protonated amino groups distribute from the matrix interface into the aqueous interior, resulting in the effective ionic interaction with platelets to increase their retention on HA copolymer surfaces. The number of protonated amino groups in polyamine portions crucially affected platelet retention. Worth noticing is that an introduction of a small but definite amount of cationic sites on the polymer surface led to significantly minimized platelet retention. It is considered that the surface property of PHEMA was drastically changed to a non-adhesive surface by introducing a small amount of protonated amino groups.