Advanced Glycation Endproducts Accelerate Calcification in Microvascular Pericytes

Vascular calcification in advanced atherosclerosis is frequently associated with diabetes, and is a predictor of future cardiovascular events. To investigate the molecular mechanisms of vascular calcification, we examined whether advanced glycation endproducts (AGE) formed at an accelerated rate und...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 1999-05, Vol.258 (2), p.353-357
Main Authors: Yamagishi, Sho-ichi, Fujimori, Hideki, Yonekura, Hideto, Tanaka, Nobushige, Yamamoto, Hiroshi
Format: Article
Language:English
Subjects:
advanced glycation end products (AGE)
Alkaline Phosphatase - genetics
Animals
atherosclerosis
Base Sequence
calcification
Calcinosis
Calcium - metabolism
Cattle
differentiation
DNA Primers
Glycation End Products, Advanced
Osteopontin
pericytes
Retinal Vessels - enzymology
Retinal Vessels - metabolism
Retinal Vessels - pathology
RNA, Messenger - genetics
RNA, Messenger - metabolism
Sialoglycoproteins - genetics
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Summary:Vascular calcification in advanced atherosclerosis is frequently associated with diabetes, and is a predictor of future cardiovascular events. To investigate the molecular mechanisms of vascular calcification, we examined whether advanced glycation endproducts (AGE) formed at an accelerated rate under diabetes induce the osteoblastic differentiation of pericytes, a mesenchymal progenitor. First, von Kossa staining demonstrated that AGE significantly increased the number of calcified nodules in a bovine pericyte culture. AGE were also found to induce calcium accumulation in the pericyte monolayer in time- and dose-dependent manners. Second, quantitative reverse transcription-polymerase chain reaction revealed that AGE increased the pericyte levels of mRNAs coding for alkaline phosphatase and osteopontin, the representative markers for early and late osteoblastic differentiation, respectively. Alkaline phosphatase activity was actually enhanced by AGE. The results suggest that AGE have the ability to induce the osteoblatic differentiation of pericytes, which would contribute to the development of vascular calcification in diabetes.
ISSN:0006-291X
1090-2104
DOI:10.1006/bbrc.1999.0625