Macrophage insulin receptor deficiency increases ER stress-induced apoptosis and necrotic core formation in advanced atherosclerotic lesions
| Autor: | Ira Tabas, Domenico Accili, Mollie Ranalletta, Tracie DeVries-Seimon, Seongah Han, Chien-Ping Liang, Carrie L. Welch, Kadesha Collins-Fletcher, Alan R. Tall |
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| Jazyk: | angličtina |
| Předmět: |
Male
medicine.medical_specialty Physiology HUMDISEASE Gene Expression Apoptosis Mice Transgenic Biology Endoplasmic Reticulum Mice Necrosis Insulin resistance Internal medicine In Situ Nick-End Labeling medicine Animals Insulin Phosphorylation Scavenger receptor Protein kinase B Molecular Biology Bone Marrow Transplantation Reverse Transcriptase Polymerase Chain Reaction Macrophages Scavenger Receptors Class A Cell Biology Atherosclerosis medicine.disease Immunohistochemistry Receptor Insulin Oncogene Protein v-akt Insulin receptor Cholesterol Endocrinology SIGNALING LDL receptor Unfolded protein response biology.protein Female Metabolic syndrome Signal transduction Foam Cells Signal Transduction |
| Zdroj: | Cell Metabolism. (4):257-266 |
| ISSN: | 1550-4131 |
| DOI: | 10.1016/j.cmet.2006.02.008 |
| Popis: | Insulin resistance in diabetes and metabolic syndrome is thought to increase susceptibility to atherosclerotic cardiovascular disease, but the underlying mechanisms are poorly understood. To evaluate the possibility that decreased insulin signaling in macrophage foam cells might worsen atherosclerosis, Ldlr(-/-) mice were transplanted with insulin receptor Insr(+/+) or Insr(-/-) bone marrow. Western diet-fed Insr(-/-) recipients developed larger, more complex lesions with increased necrotic cores and increased numbers of apoptotic cells. Insr(-/-) macrophages showed diminished Akt phosphorylation and an augmented ER stress response, leading to induction of scavenger receptor A and increased apoptosis when challenged with cholesterol loading or nutrient deprivation. These studies suggest that defective insulin signaling and reduced Akt activity impair the ability of macrophages to deal with ER stress-induced apoptosis within atherosclerotic plaques. |
| Databáze: | OpenAIRE |
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