carboprostacyclin and Arteriosclerosis

Atherosclerosis is a curious process of the intima of the vessel walls characterized by platelet aggregation, deposition of thrombotic material, lipid and fibrin which finally culminates in the intimal thickening, vascularization, and haemorrhage from the new vessels. The lipids demonstrated in the atherosclerotic plaque are mainly cholesterol, triglycerides, and phospholipids. Hyperlipidaemia initiates and maintains the atherosclerotic process and a diet rich in unsaturated essential fatty acids is known to be of benefit in arresting the process. Prostaglandins are formed from unsaturated essential fatty acids and are known to regulate platelet aggregation and thrombus formation. Thus atherosclerosis may be a disease of altered PG system and if so this would pave the way for new therapeutic strategies.

Topics: Alprostadil; Arteriosclerosis; Aspirin; Blood Vessels; Cell Membrane Permeability; Cell Survival; Cholesterol; Endothelium; Epoprostenol; Humans; Platelet Adhesiveness; Prostaglandins; Prostaglandins E; Thromboxane A2

We examined the influence of stable prostacyclin analogues (carbacyclin) and thromboxane A2 (U46619) on atherosclerotic properties of cells: [3H]thymidine incorporation and intracellular cholesterol content. A primary culture of human aortic subendothelial cells derived from atherosclerotic plaques was used. Carbacyclin exerted a direct anti-atherosclerotic effect, significantly reducing atherosclerotic manifestations of cells, while agent U46619 stimulated proliferation and cholesterol accumulation, i.e. demonstrated atherogenic potency in culture. Calcium antagonists (verapamil and diltiazem) markedly enhanced anti-atherosclerotic properties of carbacyclin and restricted the atherogenicity of U46619.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Aorta; Arteriosclerosis; Cells, Cultured; Diltiazem; DNA Replication; Epoprostenol; Humans; Muscle, Smooth, Vascular; Prostaglandin Endoperoxides, Synthetic; Prostaglandins, Synthetic; Verapamil

We investigated the effects of stable analogues of prostacyclin (carbacyclin) and thromboxane A2 (U46619) and various calcium antagonists on atherosclerotic cellular indices, intracellular cholesterol content and [3H]thymidine incorporation. Primary culture of human subendothelial cells derived from atherosclerotic plaques of aorta was used. Carbacyclin reduced cholesterol accumulation and cell proliferation. U46619 in opposite to carbacyclin stimulated this processes. In general, carbacyclin exerted a direct antiatherosclerotic and U46619 - atherogenic action in culture. Calcium antagonists: dihydropyridines, verapamil derivatives and diltiazem demonstrated antiatherosclerotic properties themselves and potentiated carbacyclin effect but restricted atherogenicity of U46619.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Aorta; Arteriosclerosis; Calcium Channel Blockers; Cells, Cultured; Cholesterol; DNA Replication; Epoprostenol; Humans; Muscle, Smooth, Vascular; Prostaglandin Endoperoxides, Synthetic

Cholera toxin, methylisobutylxanthine and prostacyclin (PGI2) analogues as well as dibutyryl cyclic AMP inhibit by 2-7-fold 3H-thymidine uptake into intimal cells isolated from atherosclerotic human aorta in primary culture. These agents also decrease cholesteryl ester and triglyceride levels and do not affect content of phospholipids and free cholesterol in cells cultured from atherosclerotic lesions.

Topics: 1-Methyl-3-isobutylxanthine; Aorta; Arteriosclerosis; Bucladesine; Cell Division; Cholera Toxin; Cyclic AMP; Epoprostenol; Humans; In Vitro Techniques; Lipids; Theophylline; Thymidine

Topics: Arteriosclerosis; Epoprostenol; Humans; Male; Middle Aged; Prostaglandins; Prostaglandins, Synthetic