Abstract
BackgroundChronic 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.Methods and ResultsTwenty-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.ConclusionsInflammation 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.
Highlights
Cardiovascular disease (CVD) is the leading cause of morbidity among patients with end-stage renal disease (ESRD), accounting for approximately 50% of deaths and 30% of hospitalisations in this population [1]
Inflammation accelerated the progression of vascular calcification (VC) in ESRD patients by disrupting the low-density lipoprotein receptor (LDLr) pathway, which may represent a novel mechanism involved in the progression of both VC and atherosclerosis
Basic Clinical Data of the Patients in the Two Groups As shown in Table 1, there were no differences in age, body weight, erythrocyte sedimentation rate (ESR), red blood cells (RBC), Hb, total protein (TP), ALB, lipid profiles, Ca, P, Ca6P, or intact parathyroid hormone (iPTH) (P.0.05) between the inflamed group and the control group
Summary
Cardiovascular disease (CVD) is the leading cause of morbidity among patients with end-stage renal disease (ESRD), accounting for approximately 50% of deaths and 30% of hospitalisations in this population [1]. Annual CVD mortality is 10–20 fold higher in ESRD patients than in the general population, and this difference is not completely explained by traditional risk factors [2]. Vascular calcification is a complicated pathological process that develops primarily within the intimal and medial layers of the artery. AMC is an active process that involves the transformation of medial vascular smooth muscle cells (VSMCs) from a fibroblastic to an osteogenic phenotype. 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
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
