title: Untangling the role of amyloid in atherosclerosis.
abstract: OBJECTIVE
  Amyloid deposits are a defining feature of several age-related and debilitating diseases. Their widespread presence in atherosclerotic plaques suggests a potential role in lesion development. This review discusses the proteins known to accumulate in atheroma and examines the evidence that amyloid-like structures activate macrophage signaling pathways linked to inflammation and prothrombotic potential.
  
  
  RESULTS
  Numerous proteins that accumulate in atherosclerotic plaques form amyloid fibrils in vivo, including apolipoproteins, beta-amyloid, and alpha1-antitrypsin. In addition, oxidation or enzymatic modification of low-density lipoproteins induces a structural reorganization of the particle, including the acquisition of amyloid-like properties. Similarly, glycation of serum albumin, as observed in diabetes, is accompanied by the formation of aggregates with all the hallmarks of amyloid. Several receptors implicated in atherogenesis modulate the fate of amyloid fibrils by mediating their clearance (scavenger receptors A and B-I), activating inflammatory signaling cascades (receptor for advanced glycation endproducts), or both (CD36). Finally, recent studies indicate that amyloid deposition accelerates diet-induced atherosclerosis in mice.
  
  
  CONCLUSIONS
  Given the substantial evidence that amyloid fibrils or preamyloidogenic species are cytotoxic, the aberrant deposition of amyloid in the intima may be pathologically important in vascular inflammation and the promotion of atherosclerosis.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Melbourne, Victoria, Australia.
authors.forename: Geoffrey J
authors.initials: GJ
authors.lastname: Howlett
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Moore
mesh_terms: D000682:Amyloid / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001053:Apolipoproteins / Q000378:metabolism; D050197:Atherosclerosis / Q000209:etiology* / Q000276:immunology / Q000378:metabolism*; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D018836:Inflammation Mediators / Q000378:metabolism; D008262:Macrophage Activation; D051379:Mice; D015398:Signal Transduction; D000515:alpha 1-Antitrypsin / Q000378:metabolism
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D001053:Apolipoproteins; D017127:Glycation End Products, Advanced; D018836:Inflammation Mediators; D000515:alpha 1-Antitrypsin