thromboxane-a2 and Coronary-Restenosis

The present review focuses on the roles of thromboxane A2 (TxA2) in arterial thrombosis, atherogenesis, vascular stent-related ischemic events and renal proteinuria. Particular emphasis is laid on therapeutic interventions targeting the TxA2 (TP) receptors and TxA2 synthase (TS), including dual TP-receptor antagonists and TS inhibitors. Their significant inhibitory efficacies on arterial thrombogenesis, atherogenesis, restenosis after stent placement, vasoconstriction and proteinuria indicate novel and improved treatments for cardiovascular and selected renal diseases. New therapeutic interventions of the TxA2 pathway may also be beneficial for patients with poor biological antiplatelet drug response, for example, to aspirin and/or clopidogrel. These new TP/TS agents offer novel improved treatments to efficiently and simultaneously interfere with thrombogenesis and atherogenesis, and to enlarge the existing panel of platelet inhibitors for efficient prophylaxis and treatment of arterial thrombosis and renal proteinuria.

Topics: Aspirin; Cardiovascular Diseases; Clopidogrel; Coronary Artery Disease; Coronary Restenosis; Humans; Kidney Diseases; Platelet Aggregation Inhibitors; Proteinuria; Receptors, Thrombin; Thrombosis; Thromboxane A2; Thromboxane-A Synthase; Ticlopidine

Topics: Arrhythmias, Cardiac; Arteriosclerosis; Biomarkers; Cholesterol, VLDL; Coronary Restenosis; Docosahexaenoic Acids; Eicosapentaenoic Acid; Humans; Hyperlipidemias; Hypertension; Liver; Reference Values; Thrombosis; Thromboxane A2

Intracoronary radiotherapy (brachytherapy) has been proposed as treatment option for in-stent restenosis. Long-term results of brachytherapy with regard to vascular integrity and vasomotor responsiveness are unknown. The purpose of the present study was to determine the vasomotor response after brachytherapy and to assess its influence on vasomotion during exercise.. Biplane quantitative coronary angiography was performed at rest and during bicycle exercise in 27 patients with coronary artery disease. Fourteen patients underwent coronary stenting and were studied 10+/-3 months after intervention (control group). Thirteen patients were treated with brachytherapy (Guidant Galileo System) for in-stent restenosis with a mean dosis of 20 Gy at 1 mm into the vessel wall and were studied 9+/-1 months after radiation (brachytherapy group). Minimal luminal area, stent area, and proximal, distal, and a reference vessel area were determined. The reference vessel showed exercise-induced vasodilation (26+/-4%, P<0.001) in both groups. Vasomotion within the stented vessel segments was abolished. In control subjects, the proximal and distal segments showed exercise-induced vasodilation (17+/-2% and 22+/-7%, respectively; P<0.005). In contrast, there was exercise-induced vasoconstriction in the proximal and distal vessel segments of the brachytherapy group (-14+/-3% and -16+/-4%, respectively; P<0.01). Sublingual nitroglycerin was associated with maximal vasodilation of the proximal and distal vessel segments in both groups.. Normal vessel segments elicit flow-mediated vasodilation during exercise. Stent implantation does not affect physiological response to exercise proximal and distal to the stent. Brachytherapy eliminates exercise-induced vasodilation, although dilatory response to nitroglycerin is maintained, suggesting endothelial dysfunction as the underlying mechanism.

Topics: Aged; Angioplasty, Balloon; Brachytherapy; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Endothelium, Vascular; Exercise; Exercise Test; Female; Hemodynamics; Humans; Male; Middle Aged; Nitric Oxide; Nitroglycerin; Platelet Aggregation; Serotonin; Stents; Thromboxane A2; Vasodilation; Vasodilator Agents; Vasomotor System