title: Inflammation disrupts the LDL receptor pathway and accelerates the progression of vascular calcification in ESRD patients.
abstract: BACKGROUND
  Chronic inflammation plays a crucial role in the progression of vascular calcification (VC). This study was designed to investigate whether the low-density lipoprotein receptor (LDLr) pathway is involved in the progression of VC in patients with end-stage renal disease (ESRD) during inflammation.
  
  
  RESULTS
  Twenty-eight ESRD patients were divided into control and inflamed groups according to plasma C-reactive protein (CRP) level. Surgically removed tissues from the radial arteries of patients receiving arteriovenostomy were used in the experiments. The expression of tumour necrosis factor-α (TNF-α) and monocyte chemotactic protein-1 (MCP-1) of the radial artery were increased in the inflamed group. Hematoxylin-eosin and alizarin red S staining revealed parallel increases in foam cell formation and calcium deposit formation in continuous cross-sections of radial arteries in the inflamed group compared to the control, which were closely correlated with increased LDLr, sterol regulatory element binding protein-2 (SREBP-2), bone morphogenetic proteins-2 (BMP-2), and collagen I protein expression, as shown by immunohistochemical and immunofluorescent staining. Confocal microscopy confirmed that inflammation enhanced the translocation of the SREBP cleavage-activating protein (SCAP)/SREBP-2 complex from the endoplasmic reticulum to the Golgi, thereby activating LDLr gene transcription. Inflammation increased alkaline phosphatase protein expression and reduced α-smooth muscle actin protein expression, contributing to the conversion of the vascular smooth muscle cells in calcified vessels from the fibroblastic to the osteogenic phenotype; osteogenic cells are the main cellular components involved in VC. Further analysis showed that the inflammation-induced disruption of the LDLr pathway was significantly associated with enhanced BMP-2 and collagen I expression.
  
  
  CONCLUSIONS
  Inflammation accelerated the progression of VC in ESRD patients by disrupting the LDLr pathway, which may represent a novel mechanism involved in the progression of both VC and atherosclerosis.
authors.affiliation: Institute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, Nanjing City, Jiangsu Province, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.forename: Kun Ling
authors.initials: KL
authors.lastname: Ma
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: D002114:Calcinosis; D018450:Disease Progression; D005455:Fluorescent Antibody Technique; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D007676:Kidney Failure, Chronic / Q000503:physiopathology*; D018613:Microscopy, Confocal; D011973:Receptors, LDL / Q000502:physiology*
chemical_list: D011973:Receptors, LDL