beraprost and Carotid-Artery-Diseases

Beraprost sodium is an orally active prostaglandin (PG)I(2) analogue, which has antiplatelet and vasodilating properties. In this study, we investigated the effects of beraprost on the expression of vascular cell adhesion molecule-1 (VCAM-1), one of the key molecules involved in atherosclerosis, in cultured vascular endothelial cells. In addition, we examined the effects of beraprost on circulating VCAM-1 level and atherosclerosis progression in patients with type 2 diabetes mellitus. Beraprost significantly decreased tumor necrosis factor-alpha (TNF-alpha)-induced VCAM-1 expression in human vascular endothelial cells. Beraprost also repressed human monocytoid U937 cell adhesion to the vascular endothelial cells. Twenty-five patients with type 2 diabetes mellitus who had atherosclerotic change of carotid arteries were enrolled for an open prospective study: 11 patients received beraprost for 3 years, while the other 14 did not. The 3-year changes of circulating VCAM-1 level, as well as those of carotid arterial intima-media thickness (IMT) were significantly lower in the patients receiving the beraprost treatment than that in the patients without the treatment. Thus, beraprost had an ability to repress the expression of VCAM-1 in human vascular endothelial cells. In addition, beraprost lowered circulating VCAM-1 level and prevented the increase of carotid IMT in patients with type 2 diabetes mellitus. Considering that circulating VCAM-1 and IMT are predictive of future vascular events, beraprost may have a beneficial effect on progression of atherosclerosis in diabetic patients.

Topics: Carotid Arteries; Carotid Artery Diseases; Cell Adhesion; Cells, Cultured; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Drug Administration Schedule; Endothelium, Vascular; Epoprostenol; Female; Humans; Male; Middle Aged; Tumor Necrosis Factor-alpha; Tunica Intima; Tunica Media; Ultrasonography; Vascular Cell Adhesion Molecule-1

Patients with carotid atheromatous lesions were prospectively studied with indium-111 platelet imaging, platelet aggregability and B-mode real-time ultrasound tests to determine the short-term effects of orally active prostacyclin analogue TRK-100 (40 micrograms, three times daily for 4 weeks). To establish baseline values, all patients underwent indium-111 platelet imaging, platelet aggregation study and B-mode ultrasound. The results were positive for carotid plaque and platelet accumulation. Visual analysis showed repeated platelet scintigrams to be unchanged in five patients without antithrombotic therapy; repeated ultrasound studies showed no change in eight of ten plaques, while one showed progression and one regression of the plaque. In five TRK-100 treated patients, five of seven lesions with platelet accumulation at the baseline became negative, and two remained unchanged during the treatment; repeated B-mode ultrasound tests indicated eight of nine plaques remained unchanged, while one showed plaque size reduction. Quantitative analysis demonstrated that, TRK-100 significantly reduced the ADP aggregation (1 microM) from 55.2 +/- 21.3% to 24.0 +/- 14.7% (+/- SD; p less than 0.05) and the platelet accumulation index (25.7 +/- 17.2% vs 10.4 +/- 10.4%; p less than 0.05). However, there was no significant reduction in plaque scores during TRK-100 therapy compared with the baseline (2.70 +/- 2.75 mm vs 2.51 +/- 2.58 mm). The data obtained suggested that short-term TRK-100 therapy has an inhibitory effect on platelet accumulation in carotid atheroma but does not cause significant changes in plaque size.

Topics: Administration, Oral; Aged; Arteriosclerosis; Blood Platelets; Carotid Artery Diseases; Epoprostenol; Female; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Thrombosis