کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2898998 | 1173108 | 2013 | 7 صفحه PDF | دانلود رایگان |
BackgroundInsulin-degrading enzyme (IDE), a protease implicated in several chronic diseases, associates with the cytoplasmic domain of the macrophage Type A scavenger receptor (SR-A). Our goal was to investigate the effect of IDE deficiency (Ide−/−) on diet-induced atherosclerosis in low density lipoprotein-deficient (Ldlr−/−) mice and on SR-A function.MethodsIrradiated Ldlr−/− or Ide−/−Ldlr−/− mice were reconstituted with wild-type or Ide−/− bone marrow and, 6 weeks later, were placed on a high-fat diet for 8 weeks.ResultsAfter 8 weeks on a high-fat diet, male Ldlr−/− recipients of Ide−/− bone marrow had more atherosclerosis, higher serum cholesterol and increased lesion-associated β-amyloid, an IDE substrate, and receptor for advanced glycation end products (RAGE), a proinflammatory receptor for β-amyloid, compared to male Ldlr−/− recipients of wild-type bone marrow. IDE deficiency in male Ldlr−/− recipient mice did not affect atherosclerosis or cholesterol levels and moderated the effects of IDE deficiency of bone marrow-derived cells. No differences were seen between Ldlr−/− and Ide−/−Ldlr−/− female mice reconstituted with Ide−/− or wild-type bone marrow. IDE deficiency in macrophages did not alter SR-A levels, cell surface SR-A, or foam cell formation.ConclusionIDE deficiency in bone marrow-derived cells results in larger atherosclerotic lesions, increased lesion-associated Aβ and RAGE, and higher serum cholesterol in male, Ldlr−/− mice.
Journal: Cardiovascular Pathology - Volume 22, Issue 6, November–December 2013, Pages 458–464