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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: OBJECTIVE, RESULTS. Meshes: Animals, Apoptosis, Atherosclerosis, Cells, Cultured, Cytochromes c, Dose-Response Relationship, Drug, Endothelial Cells, GTP Phosphohydrolases, Humans, Membrane Potential, Mitochondrial, Membrane Proteins, Mice, Inbred C57BL, Mice, Transgenic, Microtubule-Associated Proteins, Mitochondria, Mitochondrial Dynamics, Mitochondrial Membrane Transport Proteins, Mitochondrial Proteins, Oxidative Stress, Phosphatidylinositol 3-Kinase, Proto-Oncogene Proteins c-akt, Proto-Oncogene Proteins c-bcl-2, Retinol-Binding Proteins, Plasma, Signal Transduction, Superoxides, Time Factors, bcl-2-Associated X Protein.
user
Does retinol binding protein 4 induce mitochondrial dysfunction and vascular oxidative damage? Context: Mitochondrial dysfunction has been implicated in cardiovascular diseases. Elevation of serum retinol binding protein 4 (RBP4) in patients has been linked to cardiovascular disease. However, the role of RBP4 on mitochondrial oxidative stress and vascular oxidative damage is not well demonstrated. Therefore, we evaluated the impact of RBP4 on the mitochondrial reactive oxygen species (ROS) and dynamics in the pathogenesis of cardiovascular diseases. RBP4 treatment increased mitochondrial superoxide generation in a dose-dependent manner in human aortic endothelial cells (HAECs). Exposure to RBP4 also promoted mitochondrial dysfunction as determined by decreased mitochondrial content and integrity as well as membrane potential in HAECs. Incubation with RBP4 suppressed mitofusin (Mfn)-1 protein expression, but enhanced dynamin-related protein-1 (Drp1) and fission-1 (Fis1) protein expression in HAECs, suggesting an impairment of mitochondrial fusion and fission dynamics. Moreover, RBP4 treatment significantly induced endothelial apoptosis, increased the expression of Cytochrome C and Bax, but decreased the expression of Bcl-2. Furthermore, RBP4 stimulation suppressed phosphatidyl inositol 3-kinase (PI3K)/Akt signaling in HAECs. Finally, RBP4-Tg mice exhibited severe mitochondrial dysfunction and vascular oxidative damage in aorta compared with wide-type C57BL/6J mice.
assistant
The present study uncovers a novel mechanism through which RBP4 induces vascular oxidative damage and accelerates the development of atherosclerosis. Final Decision: yes