Is chronic kidney disease-mineral and bone disorder associated with the presence of endothelial progenitor cells with a calcifying phenotype?

Cianciolo, Giuseppe; Capelli, Irene; Cappuccilli, Maria; Scrivo, Anna; Donadei, Chiara; Marchetti, Antonio; Rucci, Paola; Manna, Gaetano La

doi:10.1093/ckj/sfw145

Cited by 11 publications

(8 citation statements)

References 39 publications

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“…Our circulating concentrations were similar to those reported elsewhere for CKD haemodialysis patients (33). Levels of OCN-positive circulating endothelial progenitor cells have been found to be increased in haemodialysis patients compared to controls (34). Total OCN was not however correlated with calcification scoring or carotid-femoral pulse wave velocity, a measure of arterial stiffness, in our group as a whole.…”

Section: Discussionsupporting

confidence: 90%

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: Discussionsupporting

confidence: 90%

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

et al. 2020

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“…The osteogenic markers, OC, OPN and SOST, were elevated in the NP group of patients compared to both NI and healthy controls. It is interesting that in kidney disease patients, EPCs have been reported to undergo an endothelial-to-procalcific shift, expressing mineralisation biomarkers, including OC and OPN 57 . Flammer et al .…”

Section: Discussionmentioning

confidence: 99%

Diabetic endothelial colony forming cells have the potential for restoration with glycomimetics

Langford-Smith

Hasan

Weston

et al. 2019

Sci Rep

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Endothelial colony forming progenitor cell (ECFC) function is compromised in diabetes, leading to poor vascular endothelial repair, which contributes to impaired diabetic foot ulcer healing. We have generated novel glycomimetic drugs with protective effects against endothelial dysfunction. We investigated the effect of glycomimetic C3 on the functional capacity of diabetic ECFCs. ECFCs were isolated from healthy controls and patients with diabetes with neuroischaemic (NI) or neuropathic (NP) foot ulcers. Functionally, diabetic ECFCs demonstrated delayed colony formation (p < 0.02), differential proliferative capacity (p < 0.001) and reduced NO bioavailability (NI ECFCs; p < 0.05). Chemokinetic migration and angiogenesis were also reduced in diabetic ECFCs (p < 0.01 and p < 0.001), and defects in wound closure and tube formation were apparent in NP ECFCs (p < 0.01). Differential patterns in mitochondrial activity were pronounced, with raised activity in NI and depressed activity in NP cells (p < 0.05). The application of glycomimetic improved scratch wound closure in vitro in patient ECFCs (p < 0.01), most significantly in NI cells (p < 0.001), where tube formation (p < 0.05) was also improved. We demonstrate restoration of the deficits in NI cells but not NP cells, using a novel glycomimetic agent, which may be advantageous for therapeutic cell transplantation or as a localised treatment for NI but not NP patients.

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“…Cells with an osteogenic phenotype may originate from vascular, wall-resident, mesenchymal stem cells, transdifferentiated mature or circulating VSMCs, pericytes, or circulating calcifying cells (CCCs) [33]. CCCs have been associated with coronary artery disease and calcific aortic stenosis, in both advanced CKD and diabetes [34,35,36]. Although their role is not yet fully defined, the detection and recognition of CCCs is a critical step in the understanding of CVC pathogenesis.…”

Section: Vc Is An Actively Regulated Processmentioning

confidence: 99%

The Key Role of Phosphate on Vascular Calcification

Cozzolino

Ciceri

Galassi

et al. 2019

Toxins

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115

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Vascular calcification (VC) is common in dialysis and non-dialysis chronic kidney disease (CKD) patients, even in the early stage of the disease. For this reason, it can be considered a CKD hallmark. VC contributes to cardiovascular disease (CVD) and increased mortality among CKD patients, although it has not been proven. There are more than one type of VC and every form represents a marker of systemic vascular disease and is associated with a higher prevalence of CVD in CKD patients, as shown by several clinical studies. Major risk factors for VC in CKD include: Increasing age, dialysis vintage, hyperphosphatemia (particularly in the setting of intermittent or persistent hypercalcemia), and a positive net calcium and phosphate balance. Excessive oral calcium intake, including calcium-containing phosphate binders, increases the risk for VC. Moreover, it has been demonstrated that there is less VC progression with non-calcium-containing phosphate binders. Unfortunately, until now, a specific therapy to prevent progression or to facilitate regression of VC has been found, beyond careful attention to calcium and phosphate balance.

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Is chronic kidney disease-mineral and bone disorder associated with the presence of endothelial progenitor cells with a calcifying phenotype?

Cited by 11 publications

References 39 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

Diabetic endothelial colony forming cells have the potential for restoration with glycomimetics

The Key Role of Phosphate on Vascular Calcification

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