scholarly journals RAGE Differentially Altered in vitro Responses in Vascular Smooth Muscle Cells and Adventitial Fibroblasts in Diabetes-Induced Vascular Calcification

2021 ◽  
Vol 12 ◽  
Author(s):  
Amber M. Kennon ◽  
James A. Stewart
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
P38 Mapk ◽  
Vascular Calcification ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Adventitial Fibroblasts ◽  
Rage Expression

The Advanced Glycation End-Products (AGE)/Receptor for AGEs (RAGE) signaling pathway exacerbates diabetes-mediated vascular calcification (VC) in vascular smooth muscle cells (VSMCs). Other cell types are involved in VC, such as adventitial fibroblasts (AFBs). We hope to elucidate some of the mechanisms responsible for differential signaling in diabetes-mediated VC with this work. This work utilizes RAGE knockout animals and in vitro calcification to measure calcification and protein responses. Our calcification data revealed that VSMCs calcification was AGE/RAGE dependent, yet AFBs calcification was not an AGE-mediated RAGE response. Protein expression data showed VSMCs lost their phenotype marker, α-smooth muscle actin, and had a higher RAGE expression over non-diabetics. RAGE knockout (RKO) VSMCs did not show changes in phenotype markers. P38 MAPK, a downstream RAGE-associated signaling molecule, had significantly increased activation with calcification in both diabetic and diabetic RKO VSMCs. AFBs showed a loss in myofibroblast marker, α-SMA, due to calcification treatment. RAGE expression decreased in calcified diabetic AFBs, and P38 MAPK activation significantly increased in diabetic and diabetic RKO AFBs. These findings point to potentially an alternate receptor mediating the calcification response in the absence of RAGE. Overall, VSMCs and AFBs respond differently to calcification and the application of AGEs.

Expanded Haemodialysis Therapy of Chronic Haemodialysis Patients Prevents Calcification and Apoptosis of Vascular Smooth Muscle Cells in vitro

2017 ◽  
Vol 45 (1-3) ◽  
pp. 131-138 ◽  
Author(s):  
Kevin Willy ◽  
Matthias Girndt ◽  
Jakob Voelkl ◽  
Roman Fiedler ◽  
Peter Martus ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Calcification ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Dialysis Patients ◽  
Serum Samples ◽  
Dialysis Membranes

Background: Vascular calcification is a common phenomenon in patients with chronic kidney disease and strongly associated with increased cardiovascular mortality. Vascular calcification is an active process mediated in part by inflammatory processes in vascular smooth muscle cells (VSMC). These could be modified by the insufficient removal of proinflammatory cytokines through conventional high-flux (HF) membranes. Recent trials demonstrated a reduction of inflammation in VSMC by use of dialysis membranes with a higher and steeper cut-off. These membranes caused significant albumin loss. Therefore, the effect of high retention Onset (HRO) dialysis membranes on vascular calcification and its implications in vitro was evaluated. Methods: In the PERCI II trial, 48 chronic dialysis patients were dialyzed using HF and HRO dialyzers and serum samples were collected. Calcifying VSMC were incubated with the serum samples. Calcification was determined using alizarin red staining (AZR) and determination of alkaline phosphatase (ALP) activity. Furthermore, apoptosis was evaluated, and release of matrix Gla protein (MGP), osteopontin (OPN) and growth differentiation factor 15 (GDF-15) were measured in cell supernatants. Results: Vascular calcification in vitro was significantly reduced by 24% (ALP) and 36% (AZR) after 4 weeks of HRO dialysis and by 33% (ALP) and 48% (AZR) after 12 weeks of dialysis using HRO membranes compared to HF dialysis. Apoptosis was significantly lower in the HRO group. The concentrations of MGP and OPN were significantly elevated after incubation with HF serum compared to HRO serum and healthy controls. Similarly, GDF-15 release in the supernatant was elevated after incubation with HF serum, an effect significantly ameliorated after treatment with HRO medium. Conclusions: Expanded haemodialysis therapy reduces the pro-calcific potential of serum from dialysis patients in vitro. With a markedly reduced albumin filtration compared to high cut-off dialysis, use of the HRO dialyzers may possibly provide a treatment option for chronic dialysis patients to reduce the progression of vascular calcification.

scholarly journals Development of the BioHybrid Assay: Combining Primary Human Vascular Smooth Muscle Cells and Blood to Measure Vascular Calcification Propensity

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2097
Author(s):  
Armand M. G. Jaminon ◽  
Asim C. Akbulut ◽  
Niko Rapp ◽  
Rafael Kramann ◽  
Erik A. L. Biessen ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Calcification ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Matrix Gla Protein ◽  
Plasma Samples ◽  
Cvd Risk

Background: Vascular calcification is an active process that increases cardiovascular disease (CVD) risk. There is still no consensus on an appropriate biomarker for vascular calcification. We reasoned that the biomarker for vascular calcification is the collection of all blood components that can be sensed and integrated into a calcification response by human vascular smooth muscle cells (hVSMCs). Methods: We developed a new cell-based high-content assay, the BioHybrid assay, to measure in vitro calcification. The BioHybrid assay was compared with the o-Cresolphthalein assay and the T50 assay. Serum and plasma were derived from different cohort studies including chronic kidney disease (CKD) stages III, IV, V and VD (on dialysis), pseudoxanthoma elasticum (PXE) and other cardiovascular diseases including serum from participants with mild and extensive coronary artery calcification (CAC). hVSMCs were exposed to serum and plasma samples, and in vitro calcification was measured using AlexaFluor®-546 tagged fetuin-A as calcification sensor. Results: The BioHybrid assay measured the kinetics of calcification in contrast to the endpoint o-Cresolphthalein assay. The BioHybrid assay was more sensitive to pick up differences in calcification propensity than the T50 assay as determined by measuring control as well as pre- and post-dialysis serum samples of CKD patients. The BioHybrid response increased with CKD severity. Further, the BioHybrid assay discriminated between calcification propensity of individuals with a high CAC index and individuals with a low CAC index. Patients with PXE had an increased calcification response in the BioHybrid assay as compared to both spouse and control plasma samples. Finally, vitamin K1 supplementation showed lower in vitro calcification, reflecting changes in delta Agatston scores. Lower progression within the BioHybrid and on Agatston scores was accompanied by lower dephosphorylated-uncarboxylated matrix Gla protein levels. Conclusion: The BioHybrid assay is a novel approach to determine the vascular calcification propensity of an individual and thus may add to personalised risk assessment for CVD.

scholarly journals Prevention of Vascular Calcification by Magnesium and Selected Polyphenols

2021 ◽  
Vol 2021 ◽  
pp. 1-5
Author(s):  
Haile Mehansho ◽  
Satya Majeti ◽  
Gabe Tzeghai
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Calcification ◽  
Vascular Smooth Muscle Cells ◽  
Heart Diseases ◽  
In Vitro Study ◽  
Muscle Cells ◽  
Calcium Deposition

Arterial vascular calcification (VC) represents formation of calcium phosphate deposits on the interior of arteries, which could restrict blood flow leading to heart health problems, including morbidity and mortality. VC is a complex and tightly regulated process that involves transformation of vascular smooth muscle cells (VSMCs) to bone-like cells and subsequent deposition of calcium as hydroxyapatite. Natural bioactives, including quercetin (Q), curcumin (C), resveratrol (R), and magnesium (Mg), have been reported to inhibit VC. Thus, we conducted an in vitro study using rat vascular smooth muscle cells (rVSMCs) to evaluate the protective effect of natural bioactives found in OptiCel, that is, Mg combined with polyphenols (PPs), Q, C, and R. Calcification was induced by culturing rVSMCs in a high phosphate (HP) medium. The addition of Mg and Q + C + R separately decreased the HP-induced calcium deposition by 37.55% and 42.78%, respectively. In contrast, when Mg was combined with Q, C, and R, the inhibition of calcium deposition was decreased by 92.88%, which is greater than their calculated additive inhibition (80.33%). These results demonstrate that the combination of Mg with selected PPs (Q, C, and R) is more effective than when used separately. The findings also suggest the combination has a synergistic effect in inhibiting VC, which is a risk factor for cardiovascular disease. Thus, regular consumption of these natural bioactives could have a beneficial effect in reducing the development of heart diseases.

Endothelin-1 is a potent regulator in vivo in vascular calcification and in vitro in calcification of vascular smooth muscle cells

Peptides ◽  
2003 ◽  
Vol 24 (8) ◽  
pp. 1149-1156 ◽  
Author(s):  
Sheng Ying Wu ◽  
Bao Hong Zhang ◽  
Chun Shui Pan ◽  
Hong Feng Jiang ◽  
Yong Zheng Pang ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Calcification ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Endothelin 1
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