[The effects of failure of low density lipoprotein receptor expression induced by inflammation on radial artery foam cell formation in patients with end-stage renal disease].
OBJECTIVE
To investigate whether inflammation exacerbates lipid accumulation in the radial arteries of patients with end-stage renal disease (ESRD) and to explore its underlying mechanisms.


METHODS
Thirty ESRD patients receiving arteriovenostomy were included. The patients were divided by the plasma level of C-reactive protein into control group (n = 16) and inflamed group (n = 14). Foam cell formation and lipid droplet accumulation were checked by HE staining and Oil red O staining. Tissue inflammation and intracellular cholesterol trafficking correlated proteins were examined by immunohistochemistry or immunofluorescent staining.


RESULTS
There were no differences in primary diseases, age, body weight, hemoglobin, total protein, albumin, glucose, lipid profile between the two groups (all P values >0.05). The expressions of tumor necrosis factor α (TNFα) and monocyte chemotactic protein-1 (MCP-1) of the radial artery were increased in the inflamed group. There was significant lipid accumulation in the radial arteries of inflamed group compared to the control group, which was correlated with the increased protein expressions of low density lipoprotein receptor (LDLr), sterol regulatory element binding protein-2 (SREBP-2), and SREBP cleavage-activating protein (SCAP). Confocal microscopy observation showed that inflammation enhanced the translocation of SCAP escorting SREBP-2 from endoplasmic reticulum to Golgi, thereby activating LDLr gene transcription. Further analysis showed that dysregulation of LDLr pathway induced by inflammation was associated with increased protein expression of mTOR (r = 0.733, P < 0.05), especially with the enhanced co-expression of mTOR and SREBP-2(P < 0.05).


CONCLUSIONS
Inflammation accelerates the progression of foam cell formation in ESRD patients via dysregulation of LDLr pathway, which might be partly through the activation of mTOR pathway.
Department of Nephrology, Zhongda Hospital, Southeast University, Nanjing 210009, China (Email: mmkkll@hotmail.com).
Kun-ling
KL
Ma
Jing
J
Liu
Min
M
Gao
Jie
J
Ni
Yang
Y
Zhang
Xiao-liang
XL
Zhang
Hong
H
Liu
Hai-quan
HQ
Huang
Long
L
Chen
Yan-li
YL
Wang
Bi-cheng
BC
Liu
D000328:Adult; D000368:Aged; D002097:C-Reactive Protein / Q000378:metabolism; D018932:Chemokine CCL2 / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D005487:Foam Cells / Q000166:cytology*; D006801:Humans; D007249:Inflammation; D007676:Kidney Failure, Chronic / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D017534:Radial Artery / Q000166:cytology / Q000473:pathology; D011973:Receptors, LDL / Q000378:metabolism*; D051782:Sterol Regulatory Element Binding Protein 2 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
C111835:CCL2 protein, human; D018932:Chemokine CCL2; D011973:Receptors, LDL; C497390:SREBF2 protein, human; D051782:Sterol Regulatory Element Binding Protein 2; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein