Characterisation of Calcium Phosphate Crystals on Calcified Human Aortic Vascular Smooth Muscle Cells and Potential Role of Magnesium

Louvet, Loı̈c; Bazin, Dominique; Büchel, Janine; Steppan, Sonja; Passlick–Deetjen, Jutta; Massy, Ziad A.

doi:10.1371/journal.pone.0115342

Cited by 68 publications

(49 citation statements)

References 50 publications

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“…Magnesium was tested in this study and results confirmed its beneficial role in preventing the VC process. Although previous studies already established the beneficial role of Mg 2+ and demonstrated its ability to counteract the main calcification mediators [ 21 – 24 , 38 ], the precise intracellular mode of action of Mg 2+ remains elusive. Our data suggest that Mg 2+ is able to antagonize the Pi-induced decrease of 3 miRs (miR-30b, miR-133a, and miR-143) involved in mineralization processes or SMC phenotypic switch.…”

Section: Discussionmentioning

confidence: 99%

Magnesium Attenuates Phosphate-Induced Deregulation of a MicroRNA Signature and Prevents Modulation of Smad1 and Osterix during the Course of Vascular Calcification

Louvet

Metzinger

Büchel

et al. 2016

BioMed Research International

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Vascular calcification (VC) is prevalent in patients suffering from chronic kidney disease (CKD). High phosphate levels promote VC by inducing abnormalities in mineral and bone metabolism. Previously, we demonstrated that magnesium (Mg2+) prevents inorganic phosphate- (Pi-) induced VC in human aortic vascular smooth muscle cells (HAVSMC). As microRNAs (miR) modulate gene expression, we investigated the role of miR-29b, -30b, -125b, -133a, -143, and -204 in the protective effect of Mg2+ on VC. HAVSMC were cultured in the presence of 3 mM Pi with or without 2 mM Mg2+ chloride. Total RNA was extracted after 4 h, 24 h, day 3, day 7, and day 10. miR-30b, -133a, and -143 were downregulated during the time course of Pi-induced VC, whereas the addition of Mg2+ restored (miR-30b) or improved (miR-133a, miR-143) their expression. The expression of specific targets Smad1 and Osterix was significantly increased in the presence of Pi and restored by coincubation with Mg2+. As miR-30b, miR-133a, and miR-143 are negatively regulated by Pi and restored by Mg2+ with a congruent modulation of their known targets Runx2, Smad1, and Osterix, our results provide a potential mechanistic explanation of the observed upregulation of these master switches of osteogenesis during the course of VC.

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Section: Discussionmentioning

confidence: 99%

Magnesium Attenuates Phosphate-Induced Deregulation of a MicroRNA Signature and Prevents Modulation of Smad1 and Osterix during the Course of Vascular Calcification

Louvet

Metzinger

Büchel

et al. 2016

BioMed Research International

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“…[31][32][33][34] We observed, however, that human aortic VSMCs exposed to high calcium, phosphate and magnesium concentrations in vitro stabilized CPA crystals without changing their structure and with no evidence of whitlockite crystal formation. 35 Based on this in vitro study, it is highly improbable that high magnesium concentrations alter CPA nucleation or growth by direct physicochemical interaction with the crystals. We hypothesize that the inhibitory effects of magnesium on vascular calcification occur via a cellmediated action.…”

Section: Vascular Calcificationmentioning

confidence: 98%

Magnesium and cardiovascular complications of chronic kidney disease

Massy

Drüeke

2015

Nat Rev Nephrol

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Cardiovascular complications are the leading cause of death in patients with chronic kidney disease (CKD). Abundant experimental evidence suggests a physiological role of magnesium in cardiovascular function, and clinical evidence suggests a role of the cation in cardiovascular disease in the general population. The role of magnesium in CKD-mineral and bone disorder, and in particular its impact on cardiovascular morbidity and mortality in patients with CKD, is however not well understood. Experimental studies have shown that magnesium inhibits vascular calcification, both by direct effects on the vessel wall and by indirect, systemic effects. Moreover, an increasing number of epidemiologic studies in patients with CKD have shown associations of serum magnesium levels with intermediate and hard outcomes, including vascular calcification, cardiovascular events and mortality. Intervention trials in these patients conducted to date have had small sample sizes and have been limited to the study of surrogate parameters, such as arterial stiffness, vascular calcification and atherosclerosis. Randomized controlled trials are clearly needed to determine the effects of magnesium supplementation on hard outcomes in patients with CKD.

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“…For years, people have focused on the effects of vascular implants on the proliferation and adhesion of vSMCs, but paid little attention to their roles in the vSMC phenotype modulation via altering vascular microenvironment. So far, there were a few of reports about vSMC calcification . Given the phenotypic flexibility of vSMCs, the contribution of the different vSMC phenotypes to atherosclerosis, and the rapid corrosion of magnesium, it is inevitable that the implanted Mg‐based stent materials would alter the vascular microenvironment and thus modulate the phenotypes of vSMCs at the treated vessels, and eventually affect the fate of the stent‐intervened atherosclerotic plaques.…”

Section: Introductionmentioning

confidence: 99%

Magnesium ion leachables induce a conversion of contractile vascular smooth muscle cells to an inflammatory phenotype

et al. 2018

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Phenotype switching is a characteristic response of vascular smooth muscle cells (vSMCs) to the dynamic microenvironment and contributes to all stages of atherosclerotic plaque. Here, we immersed pure magnesium and AZ31 alloy in the completed medium under cell culture condition, applied the resultant leaching extracts to the isolated contractile rat aortic vSMCs and investigated how vSMCs phenotypically responded to the degradation of the magnesium-based stent materials. vSMCs became more proliferative and migratory but underwent more apoptosis when exposed to the degradation products of pure magnesium; while the AZ31 extracts caused less cell division but more apoptosis, thus slowing cell moving and growing. Noticeably, both leaching extracts dramatically downregulated the contractile phenotypic genes at mRNA and protein levels while significantly induced the inflammatory adhesive molecules and cytokines. Exogenously added Mg ions excited similar transformations of vSMCs. With the liberation or supplementation of Mg 2+ , the expression patterns of the pro-contractile transactivator myocardin and the pro-inflammatory transcriptional factor kruppel-like factor 4 (KLF4) were reversed. Overall, the degradation of the Mg-based materials would evoke a shift of the contractile vSMCs to an inflammatory phenotype via releasing Mg ions to induce a transition from the phenotypic control of vSMCs by the myocardin to that by the KLF4.How to cite this article: Zhou Y, Liu X, Huang N, Chen Y. 2019. Magnesium ion leachables induce a conversion of contractile vascular smooth muscle cells to an inflammatory phenotype. J Biomed Mater Res Part B 2019:107B:988-1001.

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Characterisation of Calcium Phosphate Crystals on Calcified Human Aortic Vascular Smooth Muscle Cells and Potential Role of Magnesium

Cited by 68 publications

References 50 publications

Magnesium Attenuates Phosphate-Induced Deregulation of a MicroRNA Signature and Prevents Modulation of Smad1 and Osterix during the Course of Vascular Calcification

Magnesium Attenuates Phosphate-Induced Deregulation of a MicroRNA Signature and Prevents Modulation of Smad1 and Osterix during the Course of Vascular Calcification

Magnesium and cardiovascular complications of chronic kidney disease

Magnesium ion leachables induce a conversion of contractile vascular smooth muscle cells to an inflammatory phenotype

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