title: Effects of oxidized and glycated LDL on gene expression in human retinal capillary pericytes.
abstract: OBJECTIVE
  Modified (oxidized and/or glycated) low-density lipoproteins (LDLs) have been implicated in retinal pericyte loss, one of the major pathologic features of early-stage diabetic retinopathy. To delineate underlying molecular mechanisms, the present study was designed to explore the global effects of modified LDL on pericyte gene expression.
  
  
  METHODS
  Quiescent human retinal pericytes were exposed to native LDL (N-LDL), glycated LDL (G-LDL), and heavily oxidized-glycated LDL (HOG-LDL) for 24 hours, and gene expression was evaluated by DNA microarray analysis. Several of the gene responses were checked, and in each case confirmed by reverse-transcription real-time PCR.
  
  
  RESULTS
  HOG-LDL induced a gene expression pattern markedly distinct from that of N-LDL or G-LDL, whereas G-LDL elicited gene expression similar to that of N-LDL. A comparison of responses to HOG-LDL versus N-LDL revealed 60 genes with expression that varied by > or =1.7-fold. The HOG-LDL-responsive genes included members of functional pathways, such as fatty acid, eicosanoid, and cholesterol metabolism; fibrinolytic regulation; cell growth and proliferation; cell stress responses; the kinin system; and angiogenesis.
  
  
  CONCLUSIONS
  HOG-LDL elicits gene expression in retinal pericytes that may contribute to pericyte loss and other retinal abnormalities in diabetic retinopathy. Observed proapoptotic and proangiogenic responses to HOG-LDL may be of particular importance in this regard. The genes identified through these studies provide potential therapeutic targets for the prevention and treatment of diabetic retinopathy.
authors.affiliation: Section of Endocrinology and Diabetes, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Song
authors.forename: Jeremy L
authors.initials: JL
authors.lastname: Barth
authors.forename: Yongxin
authors.initials: Y
authors.lastname: Yu
authors.forename: Kangmo
authors.initials: K
authors.lastname: Lu
authors.forename: Azar
authors.initials: A
authors.lastname: Dashti
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.forename: Cynthia K
authors.initials: CK
authors.lastname: Gittinger
authors.forename: W Scott
authors.initials: WS
authors.lastname: Argraves
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Lyons
mesh_terms: D000328:Adult; D002196:Capillaries; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D017127:Glycation End Products, Advanced; D006801:Humans; D008077:Lipoproteins, LDL / Q000187:drug effects* / Q000494:pharmacology*; D020411:Oligonucleotide Array Sequence Analysis; D020286:Pericytes / Q000187:drug effects / Q000378:metabolism*; D012171:Retinal Vessels / Q000166:cytology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000093844:Glycated Proteins
chemical_list: D017127:Glycation End Products, Advanced; D008077:Lipoproteins, LDL; C031797:glycated lipoproteins, LDL; D000093844:Glycated Proteins; C099252:oxidized low density lipoprotein