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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, METHODS, RESULTS. Meshes: Adrenergic beta-Antagonists, Annexin A5, Apoptosis, Carbazoles, Carvedilol, Caspase 3, Cell-Derived Microparticles, Chlorides, Dose-Response Relationship, Drug, Drug Evaluation, Preclinical, Ferric Compounds, Flow Cytometry, Human Umbilical Vein Endothelial Cells, Humans, Iron Chelating Agents, Iron Overload, Microscopy, Electron, Scanning, Microscopy, Fluorescence, Oxidative Stress, Propanolamines, Propranolol, Reactive Oxygen Species.
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Does carvedilol protect against iron-induced microparticle generation and apoptosis of endothelial cells? Context: Increased circulating endothelial microparticles (EMPs) have been shown to associate with endothelial dysfunction. We explored the effect of iron on EMP generation by human umbilical vein endothelial cells (HUVECs) and the potential protective effect of carvedilol. FeCl 3 was added to HUVEC culture. Iron entry into cells was monitored using fluorescent microscopic imaging, while the quantity of EMPs that was released was determined by flow cytometry. The apoptosis of HUVECs was assessed by annexin V/propidium iodide assay and caspase-3 expression. Membrane bleb formation was visualized using electron microscopy. Intracellular production of reactive oxygen species (ROS) was also monitored. The effects of beta-blockers, carvedilol and propranolol on these processes were determined by co-incubation in a dose-dependent manner. Iron entry into HUVECs was not blocked by either beta-blocker. Iron induced the generation of EMPs, the formation of membrane blebs, the apoptosis of HUVECs and the production of ROS, each in a dose-dependent manner. Carvedilol, but not propranolol, ameliorated all of these processes. Our result indicates that iron induces EMP generation and apoptosis of endothelial cells in association with increased oxidative stress.
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The protective effects of carvedilol, via its antioxidant effect, may have therapeutic potential in patients with iron overload. Final Decision: yes