Insulin-degrading enzyme deficiency in bone marrow cells increases atherosclerosis in LDL receptor-deficient mice

被引：12
作者：
Caravaggio, Justin W. [1 ,2 ]
Hasu, Mirela [1 ]
MacLaren, Robin [1 ]
Thabet, Mohamed [1 ]
Raizman, Joshua E. [1 ]
Veinot, John P. [1 ,3 ]
Marcel, Yves L. [1 ,3 ]
Milne, Ross W. [1 ,3 ]
Whitman, Stewart C. [1 ,2 ,3 ]
机构：
[1] Univ Ottawa, Inst Heart, Ottawa, ON K1Y 4W7, Canada
[2] Univ Ottawa, Dept Cellular & Mol Med, Ottawa, ON K1Y 4W7, Canada
[3] Univ Ottawa, Dept Pathol & Lab Med, Ottawa, ON K1Y 4W7, Canada
来源：
CARDIOVASCULAR PATHOLOGY | 2013年 / 22卷 / 06期
关键词：
Atherosclerosis; Insulin-degrading enzyme; LDL receptor-deficient mice; Bone marrow transplantation; Amyloid; Receptor for advanced glycation end products (RAGE); BLOOD-BRAIN-BARRIER; AMYLOID PRECURSOR PROTEIN; ALZHEIMERS-DISEASE; SCAVENGER RECEPTOR; UP-REGULATION; BETA-PEPTIDE; IN-VIVO; DEGRADATION; PRODUCTS; CLEARANCE;
D O I：
10.1016/j.carpath.2013.03.006
中图分类号：
R5 [内科学];
学科分类号：
1002 ; 100201 ;
摘要：
Background: Insulin-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. Methods: Irradiated 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. Results: After 8 weeks on a high-fat diet, male Ldlr(-/-) recipients of Ide(-/-) bone marrow had more atherosclerosis, higher serum cholesterol and increased lesion-associated beta-amyloid, an IDE substrate, and receptor for advanced glycation end products (RAGE), a proinflammatory receptor for beta-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. Conclusion: IDE deficiency in bone marrow-derived cells results in larger atherosclerotic lesions, increased lesion-associated A beta and RAGE, and higher serum cholesterol in male, Ldlr(-/-) mice. (C) 2013 Elsevier Inc. All rights reserved.
引用
收藏
页码：458 / 464
页数：7
相关论文
共 47 条
  • [11] Insulin-degrading enzyme regulates the levels of insulin, amyloid β-protein, and the β-amyloid precursor protein intracellular domain in vivo
    Farris, W
    Mansourian, S
    Chang, Y
    Lindsley, L
    Eckman, EA
    Frosch, MP
    Eckman, CB
    Tanzi, RE
    Selkoe, DJ
    Guénette, S
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (07) : 4162 - 4167
  • [12] Partial loss-of-function mutations in insulin-degrading enzyme that induce diabetes also impair degradation of amyloid β-protein
    Farris, W
    Mansourian, S
    Leissring, MA
    Eckman, EA
    Bertram, L
    Eckman, CB
    Tanzi, RE
    Selkoe, DJ
    [J]. AMERICAN JOURNAL OF PATHOLOGY, 2004, 164 (04) : 1425 - 1434
  • [13] Fazio S, 1997, J LIPID RES, V38, P391
  • [14] Quantitative trait loci near the insulin-degrading enzyme (IDE) gene contribute to variation in plasma insulin levels
    Gu, HF
    Efendic, S
    Nordman, S
    Östenson, CG
    Brismar, K
    Brookes, AJ
    Prince, JA
    [J]. DIABETES, 2004, 53 (08) : 2137 - 2142
  • [15] DEGRADATION OF INTRAENDOSOMAL INSULIN BY INSULIN-DEGRADING ENZYME WITHOUT ACIDIFICATION
    HAMEL, FG
    MAHONEY, MJ
    DUCKWORTH, WC
    [J]. DIABETES, 1991, 40 (04) : 436 - 443
  • [16] Untangling the role of amyloid in atherosclerosis
    Howlett, Geoffrey J.
    Moore, Kathryn J.
    [J]. CURRENT OPINION IN LIPIDOLOGY, 2006, 17 (05) : 541 - 547
  • [17] KAYALAR C, 1989, J BIOL CHEM, V264, P8928
  • [18] Impact of Macrophage Inflammatory Protein-1α Deficiency on Atherosclerotic Lesion Formation, Hepatic Steatosis, and Adipose Tissue Expansion
    Kennedy, Arion
    Gruen, Marnie L.
    Gutierrez, Dario A.
    Surmi, Bonnie K.
    Orr, Jeb S.
    Webb, Corey D.
    Hasty, Alyssa H.
    [J]. PLOS ONE, 2012, 7 (02):
  • [19] Decreased catalytic activity of the insulin-degrading enzyme in chromosome 10-linked Alzheimer disease families
    Kim, Minji
    Hersh, Louis B.
    Leissring, Malcolm A.
    Ingelsson, Martin
    Matsui, Toshifumi
    Farris, Wesley
    Lu, Alice
    Hyman, Bradley T.
    Selkoe, Dennis J.
    Bertram, Lars
    Tanzi, Rudolph E.
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282 (11) : 7825 - 7832
  • [20] Class A scavenger receptor-mediated adhesion and internalization require distinct cytoplasmic domains
    Kosswig, N
    Rice, S
    Daugherty, A
    Post, SR
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (36) : 34219 - 34225
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