Title: The activation of mTOR pathway induced by inflammation accelerates the progression of atherosclerosis in hemodialysis patients
Abstract: Background: Our previous studies in vivo and in vitro demonstrated that inflammation accelerated the progression of atherosclerosis via the dysregulation of low lipoprotein receptor (LDLr) pathway, which was inhibited by rapamycin, an inhibitor of mammalian target of rapamycin (mTOR). This study investigated whether inflammation exacerbates lipid accumulation in the radial artery of hemodialysis patients with arteriovenostomy and its underlying mechanisms. Methods: Thirty-one hemodialysis patients receiving arteriovenostomy were included. The patients were divided into two groups by the plasma level of C-reactive protein: Control (n=16), inflamed group (n=15). Radial artery tissues were taken when the arteriovenostomy was performed on patients. Foam cell formation and lipid droplets accumulation were checked by hematoxylin–eosin staining and Oil Red O staining. Intracellular cholesterol trafficking correlated proteins were examined by immunohistochemistry and immunofluorescent staining. Results: There was significant lipid accumulation in the radial artery of the inflamed group compared to the control group, which was correlated with the increased protein expressions of 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 the endoplasmic reticulum to the Golgi, thereby activating LDLR gene transcription. Further analysis showed that dysregulation of LDLR pathway induced by inflammation was associated with the increased protein expression of mTOR, especially with the enhanced co-expression of mTOR and SREBP-2. Conclusion: Inflammation accelerated the progression of atherosclerosis in hemodialysis patients via dysregulation of the LDLR pathway, which could be partly through the activation of the mTOR pathway.
Publication Year: 2011
Publication Date: 2011-10-01
Language: en
Type: article
Indexed In: ['crossref']
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Cited By Count: 2
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