ABSTRACT
UNLABELLED: Proatherogenic factors lead to activation of endothelial cells, which symptom is an increased expression of surface adhesion molecules enabling the initiation of a local inflammatory response. 7-ketocholesterol (7-KCH) is a product of oxidation of cholesterol with proven pro-apoptotic effect on the cells of the vessel wall. So far, however, the impact of 7-KCH on surface expression of adhesion molecules has not been assessed. The aim of this study was to evaluate the influence of 7-KCH on the surface expression of adhesion molecules--intracellular adhesion molecule 1 (ICAM-1, CD 54) and .platelet endothelial cell adhesion molecule 1 (PECAM-1, CD31) on human aortic endothelial cells (HAECs). MATERIAL AND METHODS: After treatment with 7-KCH surface expression of adhesion molecules on HAEC was measured with antihuman CD31 and anti-human CD54 antibodies using flow cytometer. RESULTS: 7-KCH significantly increases percentages of CD 54 on viable HEAC, but does not affect expression of CD 31. CONCLUSION: 7-KCH may enhance the initiation of a local inflammatory response in atherosclerosis by increasing the expression of ICAM-1.
Subject(s)
Endothelial Cells/metabolism , Endothelium, Vascular/metabolism , Intercellular Adhesion Molecule-1/metabolism , Ketocholesterols/metabolism , Ketocholesterols/pharmacology , Platelet Endothelial Cell Adhesion Molecule-1/metabolism , Aorta/cytology , Cells, Cultured , Endothelial Cells/drug effects , Endothelium, Vascular/drug effects , Humans , Platelet Endothelial Cell Adhesion Molecule-1/drug effectsABSTRACT
For many years atherosclerosis was believed to be the passive accumulation of cholesterol in vessel walls. Today the picture is more complex, as immune processes occur in atherogenesis. Considerable attention is focused on the particular role of adaptive immune responses orchestrated by T cell subsets. Since the role of Th1/Th2 balance and Th1 cell domination in atherogenesis is already known, the involvement of regulatory T lymphocytes and recently described Th17 cells raises new concerns. On one hand, each of these cells may specifically drive responses of vascular wall tissues and immune cells; however, they are subject to the control of a plethora of tissue- and pathogen-derived agents. Due to ineffective tissue regeneration, remodeling of the vascular wall occurs. The understanding of the immune regulatory network gives perspectives of innovative immunomodulatory therapies of atherosclerosis and the prevention of its complications, such as coronary artery disease.
ABSTRACT
Atrial fibrillation (AF) is the most common cardiac arrhythmia in the daily medical practice associated with increased cardiovascular mortality and stroke. Till now amiodarone is generally considered as the agent with the best efficacy for maintaining sinus rhythm. Despite its efficacy, amiodarone use is often limited by its extensive side effect profile. Dronedarone is benzofuran derivative structurally similar to amiodarone. Due to modification of the chemical structure of amiodarone the new pharmacokinetic properties provide with safety of the treatment. The ATHENA trial showed significant reductions in all-cause mortality and cardiovascular hospitalization with dronedarone use. A post hoc analysis of the ATHENA data also suggested a decrease in stroke risk with this agent. Dronedarone is efficient in the controlling of ventricular rate as well as maintaining sinus rhythm in AF contraindicated in patients with NYHA class III/IV heart failure. Dronedarone use is significantly safer however is less effective in maintaining sinus rhythm than amiodarone. The European Society of Cardiology recommends dronedarone in new Guidelines for the Management of AF as a drug of fist-line treatment, what means the new interesting and safe alternative in the treatment of AF.
