Widespread increase in myeloid calcifying cells contributes to ectopic vascular calcification in type 2 diabetes.
Circ Res
; 108(9): 1112-21, 2011 Apr 29.
Article
em En
| MEDLINE
| ID: mdl-21393578
ABSTRACT
RATIONALE Acquisition of a procalcific phenotype by resident or circulating cells is important for calcification of atherosclerotic plaques, which is common in diabetes. OBJECTIVE:
We aim to identify and characterize circulating calcifying cells, and to delineate a pathophysiological role for these cells in type 2 diabetes. METHODS ANDRESULTS:
We demonstrate for the first time that a distinct subpopulation of circulating cells expressing osteocalcin and bone alkaline phosphatase (OC(+)BAP(+)) has procalcific activity in vitro and in vivo. The study of naïve patients with chronic myeloid leukemia indicated that OC(+)BAP(+) cells have a myeloid origin. Myeloid calcifying OC(+)BAP(+) cells (MCCs) could be differentiated from peripheral blood mononuclear cells, and generation of MCCs was closely associated with expression of the osteogenic transcription factor Runx2. In gender-mismatched bone marrow-transplanted humans, circulating MCCs had a much longer half-life compared with OC(-)BAP(-) cells, suggesting they belong to a stable cell repertoire. The percentage of MCCs was higher in peripheral blood and bone marrow of type 2 diabetic patients compared with controls but was lowered toward normal levels by optimization of glycemic control. Furthermore, diabetic carotid endoarterectomy specimens showed higher degree of calcification and amounts of cells expressing OC and BAP in the α-smooth muscle actin-negative areas surrounding calcified nodules, where CD68(+) macrophages colocalize. High glucose increased calcification by MCCs in vitro, and hypoxia may regulate MCC generation in vitro and in vivo.CONCLUSIONS:
These data identify a novel type of blood-derived procalcific cells potentially involved in atherosclerotic calcification of diabetic patients.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Calcinose
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Doenças das Artérias Carótidas
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Células Mieloides
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Diabetes Mellitus Tipo 2
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Angiopatias Diabéticas
Tipo de estudo:
Clinical_trials
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Prognostic_studies
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article