Widespread Increase in Myeloid Calcifying Cells Contributes to Ectopic Vascular Calcification in Type 2 Diabetes

Fadini, Gian Paolo; Albiero, Mattia; Menegazzo, Lisa; Boscaro, Elisa; Kreutzenberg, Saula Vigili de; Agostini, Carlo; Cabrelle, Anna; Binotto, Gianni; Rattazzi, Marcello; Bertacco, Elisa; Bertorelle, Roberta; Biasini, Lorena; Mion, Monica; Plebani, Mario; Ceolotto, Giulio; Angelini, Annalisa; Castellani, Chiara; Menegolo, Mirko; Grego, Franco; Dimmeler, Stefanie; Seeger, Florian; Zeiher, Andreas M.; Tiengo, Antonio; Avogaro, Angelo

doi:10.1161/circresaha.110.234088

Cited by 106 publications

(113 citation statements)

References 31 publications

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“…Several distinct phenotypes of these circulating calcifying cells have been so far identified and characterized [5]. A specific subpopulation of circulating calcifying cells of myeloid origin, expressing OCN and BAP is increase in the bloodstream of diabetic subjects [27] and actively participate in the amplification of vascular damage [20]. In our population of osteoporotic women treated with Atorvastatin, we found a trend reduction in the number of [17] and to correlate with the presence of arterial stiffness in this clinical condition [19].…”

Section: Discussionmentioning

confidence: 58%

Atorvastatin Reduces Circulating Osteoprogenitor Cells and T‐Cell RANKL Expression in Osteoporotic Women: Implications for the Bone–Vascular Axis

Rattazzi

Faggin

Buso

et al. 2016

Cardiovascular Therapeutics

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SUMMARYAim: Circulating osteoprogenitors and receptor activator of nuclear factor kappa-B ligand (RANKL) expression in immune cells have been implicated in the pathogenesis of osteoporosis and vascular calcification. The role played by statin therapy in the bone-vascular axis is unknown. Methods: Twenty na€ ıve postmenopausal osteoporotic hypercholesterolemic women were treated with Atorvastatin 40 mg/day for 3 months. Gene expression analysis was performed to assess modification in osteoprotegerin (OPG)/RANK/RANKL expression in isolated T cells and monocytes. A flow cytometry analysis was used to study changes in the levels of circulating osteoprogenitor cells. Results: After 3 months of treatment, Atorvastatin significantly reduced total cholesterol and LDL-C, without affecting HDL-C and triglycerides. Among circulating bone and phosphocalcium homeostasis markers, we found a significant increase in OPG levels (P < 0.01) and a modest reduction in osteocalcin (OCN) (P < 0.05). We also observed a significant reduction in RANKL expression in T cells (P < 0.05). No differences were found in the expression of RANK in T cells and RANKL and RANK in monocytes. OPG expression was low in both immune cell types and was not affected by the treatment. As for circulating osteoprogenitors, we found a significant reduction of CD34 + BAP + (P < 0.05) and CD34 + OCN + BAP + (P < 0.05) cells. In vitro studies showed that Atorvastatin reduced RANKL expression in activated human T-lymphoblastoid cells (Jurkat cell line). Conclusions: Three-month Atorvastatin treatment leads to a reduction in circulating osteoprogenitor cells and RANKL expression in T cells, as well as increase in OPG serum levels. These data suggest that statins could have protective effects in the bone-vascular axis.

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Section: Discussionmentioning

confidence: 58%

Atorvastatin Reduces Circulating Osteoprogenitor Cells and T‐Cell RANKL Expression in Osteoporotic Women: Implications for the Bone–Vascular Axis

Rattazzi

Faggin

Buso

et al. 2016

Cardiovascular Therapeutics

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“…24 A weakness of our method is that, as a serum test, it does not by nature take into account the established contribution of cells, including vascular smooth muscle cells 25 and calcifying myeloid cells, 26 in promoting vascular calcifications in vivo. [27][28][29][30] Because serum represents the endogenous milieu surrounding all cells in the body, however, investigating possible CPP-cell interactions will likely also broaden our understanding of calcification processes in vivo.…”

Section: Discussionmentioning

confidence: 99%

Nanoparticle-Based Test Measures Overall Propensity for Calcification in Serum

Pasch

Farese

Gräber

et al. 2012

Journal of the American Society of Nephrology

280

372

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Vascular and soft tissue calcification contributes to cardiovascular morbidity and mortality in both the general population and CKD. Because calcium and phosphate serum concentrations are near supersaturation, the balance of inhibitors and promoters critically influences the development of calcification. An assay that measures the overall propensity for calcification to occur in serum may have clinical use. Here, we describe a nanoparticle-based assay that detects, in the presence of artificially elevated calcium and phosphate concentrations, the spontaneous transformation of spherical colloidal primary calciprotein particles (CPPs) to elongate crystalline secondary CPPs. We used characteristics of this transition to describe the intrinsic capacity of serum to inhibit the precipitation of calcium and phosphate. Using this assay, we found that both the sera of mice deficient in fetuin-A, a serum protein that inhibits calcification, and the sera of patients on hemodialysis have reduced intrinsic properties to inhibit calcification. In summary, we developed a nanoparticle-based test that measures the overall propensity for calcification in serum. The clinical use of the test requires evaluation in a prospective study.

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“…CPP clearance by macrophages may drive these cells into the calcifying myeloic cell type that was recently described in several publications. 56,57 …”

Section: Discussionmentioning

confidence: 99%

Clearance of Fetuin-A–Containing Calciprotein Particles Is Mediated by Scavenger Receptor-A

Herrmann

Schäfer²,

Heiss³

et al. 2012

Circulation Research

143

118

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Rationale: Fetuin-A is a liver-derived plasma protein involved in the regulation of calcified matrix metabolism.Biochemical studies showed that fetuin-A is essential for the formation of protein-mineral complexes, called calciprotein particles (CPPs). CPPs must be cleared from circulation to prevent local deposition and pathological calcification.Objective: We studied CPP clearance in mice and in cell culture to identify the tissues, cells, and receptors involved in the clearance. Methods and Results:

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Widespread Increase in Myeloid Calcifying Cells Contributes to Ectopic Vascular Calcification in Type 2 Diabetes

Cited by 106 publications

References 31 publications

Atorvastatin Reduces Circulating Osteoprogenitor Cells and T‐Cell RANKL Expression in Osteoporotic Women: Implications for the Bone–Vascular Axis

Atorvastatin Reduces Circulating Osteoprogenitor Cells and T‐Cell RANKL Expression in Osteoporotic Women: Implications for the Bone–Vascular Axis

Nanoparticle-Based Test Measures Overall Propensity for Calcification in Serum

Clearance of Fetuin-A–Containing Calciprotein Particles Is Mediated by Scavenger Receptor-A

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