title: Deficiency of the complement regulatory protein CD59 accelerates the development of diabetes-induced atherosclerosis in mice.
abstract: OBJECTIVE
  Clinical and experimental evidence supports a strong link between the complement system, complement regulatory proteins and the pathogenesis of diabetes vascular complications. We previously reported that the complement regulatory protein CD59 is inactivated by glycation in humans with diabetes. Our objective for this study is to assess experimentally how the deficiency of CD59 impacts the development of diabetic atherosclerosis in vivo.
  
  
  METHODS
  We crossed mCD59 sufficient and deficient mice into the ApoE-/-background to generate mCd59ab+/+/ApoE-/-and mCd59ab-/-/ApoE-/-mice, and induced diabetes by multiple low dose injections of streptozotocin. Atherosclerosis was detected by hematoxylin and eosin (H&E) and oil red-O staining. Membrane attack complex (MAC) deposition and macrophage infiltration were detected by immunostaining.
  
  
  RESULTS
  Diabetic mCD59 deficient (mCD59ab-/-/ApoE-/-) mice developed nearly 100% larger atherosclerotic lesion areas in the aorta (7.5%±0.6 vs 3.6%±0.7; p<0.005) and in the aortic roots (H&E: 26.2%±1.9 vs. 14.3%±1.1; p<0.005), in both cases associated with increased lipid (Oil red-O: 14.9%±1.1 vs. 7.8%±1.1; p<0.05) and MAC deposition (6.8%±0.8 vs. 3.0%±0.7; p<0.005) and macrophage infiltration (31.5%±3.7 vs. 16.4%±3.0; p<0.05) in the aortic roots as compared to their diabetic mCD59 sufficient (mCD59ab+/+/ApoE-/-) counterpart.
  
  
  CONCLUSIONS
  The deficiency of CD59 accelerates the development of diabetic atherosclerosis.
authors.affiliation: Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Fengming
authors.initials: F
authors.lastname: Liu
authors.affiliation: Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Rupam
authors.initials: R
authors.lastname: Sahoo
authors.affiliation: Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Ge
authors.affiliation: Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Wu
authors.affiliation: Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Pamela
authors.initials: P
authors.lastname: Ghosh
authors.affiliation: Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Xuebin
authors.initials: X
authors.lastname: Qin
authors.affiliation: Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: jhalperin@partners.org.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Halperin
mesh_terms: D000818:Animals; D001011:Aorta; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism*; D050197:Atherosclerosis / Q000150:complications / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D001786:Blood Glucose / Q000032:analysis; D018957:CD59 Antigens / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D003167:Complement Activation / Q000187:drug effects; D015938:Complement Membrane Attack Complex / Q000378:metabolism; D003433:Crosses, Genetic; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000139:chemically induced / Q000150:complications*; D003925:Diabetic Angiopathies / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D050356:Lipid Metabolism / Q000187:drug effects; D008262:Macrophage Activation / Q000187:drug effects; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013311:Streptozocin / Q000633:toxicity
chemical_list: D001057:Apolipoproteins E; D001786:Blood Glucose; D018957:CD59 Antigens; C539311:CD59a protein, mouse; C539312:CD59b protein, mouse; D015938:Complement Membrane Attack Complex; D013311:Streptozocin
keywords: Atherosclerosis; CD59; Complement; Diabetes; Diabetic vascular complications; Membrane attack complex