title: Effect of the oxLDL binding protein Fc-CD68 on plaque extension and vulnerability in atherosclerosis.
abstract: BACKGROUND
  There is strong evidence that oxidative modification of low-density lipoprotein (oxLDL) plays a critical role in atherogenesis and that oxLDL may profoundly influence the mechanical stability of atherosclerotic plaques.
  
  
  OBJECTIVE
  To block oxLDL, we designed, expressed, and tested Fc-CD68, a soluble oxLDL binding protein consisting of human Fc and the extracellular domain of the human oxLDL-binding receptor CD68.
  
  
  RESULTS
  Fc-CD68 bound with high specific affinity to oxLDL and strongly bound and colocalized with oxLDL in plaques. To study the effects of repeated administrations of Fc-CD68 on the progression of atherosclerosis and plaque vulnerability, 12- and 16-week old cholesterol-fed ApoE(-/-) mice received either Fc-CD68 (n = 6) or Fc control protein (n = 6 to 8) thrice weekly for 4 weeks. Macroscopic and histological analysis of Sudan red lipid staining showed strong and significant reduction of plaque extension in the aorta and in the aortic root, respectively. Histological analysis of pentachrome- and Sirius-stained sections of the brachiocephalic arteries of 20 week-old ApoE(-/-) mice revealed that Fc-CD68 significantly reduced the occurrence of spontaneous ruptures of established plaques by ≈20%, compared with Fc and drastically increased the collagen content of plaques. Furthermore, in immunostained sections of the brachiocephalic artery and the aortic root, Fc-CD68 reduced the infiltration of plaques with T lymphocytes, and macrophages by ≈50% and 30%, respectively.
  
  
  CONCLUSIONS
  The oxLDL binding protein Fc-CD68 attenuates atherosclerosis and strengthens the stability of atherosclerotic plaques.
authors.affiliation: Corimmun GmbH, University of Ulm, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Zeibig
authors.forename: Zhongmin
authors.initials: Z
authors.lastname: Li
authors.forename: Silvia
authors.initials: S
authors.lastname: Wagner
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Holthoff
authors.forename: Martin
authors.initials: M
authors.lastname: Ungerer
authors.forename: Andreas
authors.initials: A
authors.lastname: Bültmann
authors.forename: Kerstin
authors.initials: K
authors.lastname: Uhland
authors.forename: Jasmin
authors.initials: J
authors.lastname: Vogelmann
authors.forename: Thomas
authors.initials: T
authors.lastname: Simmet
authors.forename: Meinrad
authors.initials: M
authors.lastname: Gawaz
authors.forename: Götz
authors.initials: G
authors.lastname: Münch
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics*; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics*; D001011:Aorta / Q000187:drug effects / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology*; D001667:Binding, Competitive; D016122:Brachiocephalic Trunk / Q000187:drug effects* / Q000473:pathology*; D002352:Carrier Proteins / Q000378:metabolism / Q000494:pharmacology; D003094:Collagen / Q000378:metabolism; D018450:Disease Progression; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000235:genetics*; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D050356:Lipid Metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D008264:Macrophages / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D058226:Plaque, Atherosclerotic / Q000378:metabolism / Q000473:pathology*; D011993:Recombinant Fusion Proteins / Q000378:metabolism / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000473:pathology; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D001057:Apolipoproteins E; D002352:Carrier Proteins; D003094:Collagen; D007141:Immunoglobulin Fc Fragments; D008077:Lipoproteins, LDL; D011993:Recombinant Fusion Proteins; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C099252:oxidized low density lipoprotein