Interleukin-1β Is a Key Biomarker and Mediator of Inflammatory Vascular Calcification

Shobeiri, Navid; Bendeck, Michelle P.

doi:10.1161/atvbaha.116.308724

Cited by 22 publications

(13 citation statements)

References 26 publications

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“…Our examination of IL-1β and MMP-3 secretion revealed some interesting insights. IL-1β has emerged in recent years as a potential stimulator of vascular calcification for example by increasing ALP activity, and has been proposed as a marker of inflammatory calcification (29,42). In contrast, we found significantly increased secretion of IL-1β over time in control cells only, compared to mineralisation media treated cells.…”

Section: Discussioncontrasting

confidence: 73%

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An Investigation Into the Role of Osteocalcin in Human Arterial Smooth Muscle Cell Calcification

et al. 2020

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Osteocalcin (OCN) is a bone-derived protein that is detected within human calcified vascular tissue. Calcification is particularly prevalent in chronic kidney disease (CKD) patients but the role of OCN in calcification, whether active or passive, has not been elucidated. Part 1: The relationship between OCN, CKD and vascular calcification was assessed in CKD patients (n = 28) and age-matched controls (n = 19). Part 2: in vitro, we analyzed whether addition of uncarboxylated osteocalcin (ucOCN) influenced the rate or extent of vascular smooth muscle cell (VSMC) calcification. Human aortic VSMCs were cultured in control media or mineralisation inducing media (MM) containing increased phosphate with or without ucOCN (10 or 30 ng/mL) for up to 21 days. Markers of osteogenic differentiation and calcification were determined [alkaline phosphatase (ALP) activity, total intracellular OCN, Runx2 expression, α-SMA expression, alizarin red calcium staining, and calcium quantification]. Part 1 results: In our human population, calcification was present (mean age 76 years), but no differences were detected between CKD patients and controls. Plasma total OCN was increased in CKD patients compared to controls (14 vs. 9 ng/mL; p < 0.05) and correlated to estimated glomerular filtration rate (p < 0.05), however no relationship was detected between total OCN and calcification. Part 2 results: in vitro, ALP activity, α-SMA expression and calcium concentrations were significantly increased in MM treated VSMCs at day 21, but no effect of ucOCN was observed. Cells treated with control media+ucOCN for 21 days did not show increases in ALP activity nor calcification. In summary, although plasma total OCN was increased in CKD patients, this study did not find a relationship between OCN and calcification in CKD and non-CKD patients, and found no in vitro evidence of an active role of ucOCN in vascular calcification as assessed over 21 days. ucOCN appears not to be a mediator of vascular calcification, but further investigation is warranted.

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Section: Discussioncontrasting

confidence: 73%

“…MMP-3 and IL-1β are associated with vascular calcification (29,30). MMP-3 secretion increased with time in control media treated cells, and was increased compared to MM treated cells at day 21 (p < 0.0001; Figure 3E).…”

Section: No Differences Are Detected In Secreted Mmp-3 and Il-1β Concmentioning

confidence: 92%

An Investigation Into the Role of Osteocalcin in Human Arterial Smooth Muscle Cell Calcification

et al. 2020

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“…The NLRP3 inflammasome pathway plays a key role in this context. This multiprotein oligomer is responsible for the caspase 1-dependent release of IL-1β, a pro-inflammatory cytokine recognized as a key biomarker and mediator of inflammatory calcification [49]. Indeed, IL1-β favours VSMC osteogenic differentiation and subsequent calcification in vitro [50,51] and aortic calcifications can be inhibited by IL-1β monoclonal antibody in LDLR-deficient mice [52].…”

Section: Monocytes/macrophages and Cvcmentioning

confidence: 99%

New Insights into the Roles of Monocytes/Macrophages in Cardiovascular Calcification Associated with Chronic Kidney Disease

Hénaut¹,

Candellier

Boudot³

et al. 2019

Toxins

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Cardiovascular disease (CVD) is an important cause of death in patients with chronic kidney disease (CKD), and cardiovascular calcification (CVC) is one of the strongest predictors of CVD in this population. Cardiovascular calcification results from complex cellular interactions involving the endothelium, vascular/valvular cells (i.e., vascular smooth muscle cells, valvular interstitial cells and resident fibroblasts), and monocyte-derived macrophages. Indeed, the production of pro-inflammatory cytokines and oxidative stress by monocyte-derived macrophages is responsible for the osteogenic transformation and mineralization of vascular/valvular cells. However, monocytes/macrophages show the ability to modify their phenotype, and consequently their functions, when facing environmental modifications. This plasticity complicates efforts to understand the pathogenesis of CVC—particularly in a CKD setting, where both uraemic toxins and CKD treatment may affect monocyte/macrophage functions and thereby influence CVC. Here, we review (i) the mechanisms by which each monocyte/macrophage subset either promotes or prevents CVC, and (ii) how both uraemic toxins and CKD therapies might affect these monocyte/macrophage functions.

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“…Vascular calcification (VC) is prevalent in coronary artery disease, and its extent predicts cardiovascular risk [1]. Causes of calcification in atherosclerosis include dysregulated matrix metabolism, epitaxial mineral deposition, inflammation, oxidative stress, and apoptosis [2]. VC is mainly mediated by vascular smooth muscle cells (VSMCs) [3] whose transformation from a contractile to osteogenic phenotype promotes the process of VC [4].…”

Section: Introductionmentioning

confidence: 99%

Melatonin Attenuates Calcium Deposition from Vascular Smooth Muscle Cells by Activating Mitochondrial Fusion and Mitophagy via an AMPK/OPA1 Signaling Pathway

Chen

Zhou

Yang

et al. 2020

Oxidative Medicine and Cellular Longevity

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Mitochondrial fusion/mitophagy plays a role in cardiovascular calcification. Melatonin has been shown to protect against cardiovascular disease. This study sought to explore whether melatonin attenuates vascular calcification by regulating mitochondrial fusion/mitophagy via the AMP-activated protein kinase/optic atrophy 1 (AMPK/OPA1) signaling pathway. The effects of melatonin on vascular calcification were investigated in vascular smooth muscle cells (VSMCs). Calcium deposits were visualized by Alizarin Red S staining, while calcium content and alkaline phosphatase (ALP) activity were used to evaluate osteogenic differentiation. Western blots were used to measure expression of runt-related transcription factor 2 (Runx2), mitofusin 2 (Mfn2), mito-light chain 3 (mito-LC3) II, and cleaved caspase 3. Melatonin markedly reduced calcium deposition and ALP activity. Runx2 and cleaved caspase 3 were downregulated in response to melatonin, whereas Mfn2 and mito-LC3II were enhanced and accompanied by decreased mitochondrial superoxide levels. Melatonin also maintained mitochondrial function and promoted mitochondrial fusion/mitophagy via the OPA1 pathway. However, OPA1 deletion abolished the protective effects of melatonin on VSMC calcification. Melatonin treatment significantly increased p-AMPK and OPA1 protein expression, whereas treatment with compound C ablated the observed benefits of melatonin treatment. Collectively, our results demonstrate that melatonin protects VSMCs against calcification by promoting mitochondrial fusion/mitophagy via the AMPK/OPA1 pathway.

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Interleukin-1β Is a Key Biomarker and Mediator of Inflammatory Vascular Calcification

Cited by 22 publications

References 26 publications

An Investigation Into the Role of Osteocalcin in Human Arterial Smooth Muscle Cell Calcification

An Investigation Into the Role of Osteocalcin in Human Arterial Smooth Muscle Cell Calcification

New Insights into the Roles of Monocytes/Macrophages in Cardiovascular Calcification Associated with Chronic Kidney Disease

Melatonin Attenuates Calcium Deposition from Vascular Smooth Muscle Cells by Activating Mitochondrial Fusion and Mitophagy via an AMPK/OPA1 Signaling Pathway

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