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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, Aorta, Apolipoproteins E, Apoptosis, Body Weight, Bone Marrow Transplantation, Cholesterol, Dietary, Disease Models, Animal, Elastic Tissue, Foam Cells, Hyperlipidemias, Immunohistochemistry, Lipoproteins, MAP Kinase Kinase Kinase 5, Macrophages, Peritoneal, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Necrosis, Plaque, Atherosclerotic, Signal Transduction.
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Does apoptosis signal-regulating kinase 1 deficiency accelerate hyperlipidemia-induced atheromatous plaques via suppression of macrophage apoptosis? Context: The pathogenic role of macrophage apoptosis in atherosclerosis is still debatable, but it is considered to be a suppressor of plaque progression in early stages but a promoter of plaque necrosis in advanced stages. Apoptosis signal-regulating kinase 1 (ASK1) is a mitogen-activated protein kinase kinase kinase that plays a pivotal role in stress-induced apoptosis. In the current study, we investigated the functions of ASK1 in hyperlipidemia-induced atherosclerosis. We generated ASK1 and apolipoprotein E (apoE) double-knockout mice (ASK1(-/-)/apoE(-/-)) and analyzed atherosclerosis in ASK1(-/-)/apoE(-/-) mice fed a high-cholesterol diet for 12 weeks. ASK1(-/-)/apoE(-/-) mice had accelerated hyperlipidemia-induced atherosclerosis, which was characterized by less apoptosis of macrophages and fewer necrotic areas, and more macrophages and elastolysis compared with apoE(-/-) mice. Bone marrow transplantation from ASK1(-/-) or wild-type to apoE(-/-) mice confirmed the above observation that the recipient mice of ASK1(-/-) donors had more pronounced hyperlipidemia-induced atherosclerosis than recipient mice of wild-type donors.
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These findings suggest that ASK1 suppresses hyperlipidemia-induced atherosclerosis via increased macrophage apoptosis and that ASK1 may cause pronounced plaque vulnerability via necrotic core development. Final Decision: yes