title: Activation of mTOR contributes to foam cell formation in the radial arteries of patients with end-stage renal disease.
abstract: BACKGROUND
  Our previous in-vivo and in-vitro studies demonstrated that inflammation accelerated the progression of atherosclerosis via the dysregulation of the low-density lipoprotein receptor (LDLr) pathway. The current study aimed to investigate the effects and their underlying mechanisms of inflammation on lipid accumulation in the radial arteries of endstage renal disease (ESRD) patients with arteriovenostomy.
  
  
  METHODS
  30 ESRD patients with arteriovenostomy were included. The patients were divided into two groups based on their plasma levels of C-reactive protein: a control (n = 16) and an inflamed group (n = 14). The expression of tumor necrosis factor-alpha (TNF-alpha) and monocyte chemotactic protein-1 of the radial arteries were increased in the inflamed group. Foam cell formation and lipid droplet accumulation were examined by hematoxylin and eosin (H & E) and Oil Red O staining. Intracellular cholesterol trafficking-related proteins were examined by immunohistochemistry and immunofluorescent staining.
  
  
  RESULTS
  There was significant lipid accumulation in the radial arteries of the inflamed group compared with the control. Further analysis demonstrated that this accumulation was correlated with the increased protein expression of LDLr, sterol regulatory element-binding protein-2 (SREBP-2), and SREBP cleavageactivating protein (SCAP). Confocal microscopy showed that inflammation enhanced the translocation of SCAP escorting SREBP-2 from the endoplasmic reticulum to the Golgi, thereby activating LDLr gene transcription. Interestingly, upregulated LDLr expression was positively associated with the increased protein expression of mammalian target of rapamycin (mTOR), which had enhanced coexpression with SREBP-2. This finding suggests that the activation of mTOR may be involved in LDLr pathway disruption through the upregulation of SREBP-2 expression.
  
  
  CONCLUSIONS
  Inflammation contributed to foam cell formation in the radial arteries of ESRD patients via the dysregulation of the LDLr pathway, which could be modulated by the activation of the mTOR pathway.
authors.forename: Kun Ling
authors.initials: KL
authors.lastname: Ma
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.forename: Min
authors.initials: M
authors.lastname: Gao
authors.forename: Chang Xian
authors.initials: CX
authors.lastname: Wang
authors.forename: Jie
authors.initials: J
authors.lastname: Ni
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xiao Liang
authors.initials: XL
authors.lastname: Zhang
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.forename: Yan Li
authors.initials: YL
authors.lastname: Wang
authors.forename: Bi Cheng
authors.initials: BC
authors.lastname: Liu
mesh_terms: D000328:Adult; D000368:Aged; D050197:Atherosclerosis / Q000097:blood / Q000201:enzymology* / Q000473:pathology; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D016022:Case-Control Studies; D018932:Chemokine CCL2 / Q000032:analysis; D004789:Enzyme Activation; D005487:Foam Cells / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D007676:Kidney Failure, Chronic / Q000097:blood / Q000201:enzymology* / Q000473:pathology / Q000628:therapy; D008875:Middle Aged; D017534:Radial Artery / Q000201:enzymology* / Q000473:pathology; D011973:Receptors, LDL / Q000032:analysis; D006435:Renal Dialysis; D058570:TOR Serine-Threonine Kinases / Q000032:analysis*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D015415:Biomarkers; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D018836:Inflammation Mediators; C573412:LDLR protein, human; D011973:Receptors, LDL; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases