AIMS: Human atheroma calcification occurs secondary to repetitive injury/remodelling of the vessel wall and might be initiated by adherence of mineral-loaded fetuin-A whether or not professional matrix mineralizing cells are present. The aim was to investigate the contribution of fibroblast growth factor (FGF)-23 to ectopic mineralization. METHODS AND RESULTS: Serial sections of formalin-fixed paraffin-embedded human carotid atheroma (n = 54) were investigated with respect to (i) size and distribution of calcific deposits, (ii) indicators of chondrogenic/osteogenic transformation, and (iii) expression of fetuin-A and FGF-23. All specimens were calcified and SOX-9, collagen type II, cathepsin-K, fetuin-A and FGF-23 expression was seen in 46, 53, 53, 54 and 48 specimens, respectively. The intracellular detection of FGF-23 (45/48) indicates local synthesis. Whereas fetuin-A expression was seen also within areas of vascular smooth muscle actin-positive cells adjacent to calcific deposits, FGF-23 expression was apparently restricted to the mineralization-prone areas. Both local expression and FGF-23 serum concentrations were significantly associated with the degree of atheroma calcification. CONCLUSIONS: Besides the induction of bone islets and subsequent mineral deposition, severe remodelling of the vessel wall is sufficient to create a mineralizable fetuin-A-attracting microenvironment. FGF-23 might contribute to the formation of proper mineral, i.e. control local phosphate concentration.
AIMS: Humanatheroma calcification occurs secondary to repetitive injury/remodelling of the vessel wall and might be initiated by adherence of mineral-loaded fetuin-A whether or not professional matrix mineralizing cells are present. The aim was to investigate the contribution of fibroblast growth factor (FGF)-23 to ectopic mineralization. METHODS AND RESULTS: Serial sections of formalin-fixed paraffin-embedded human carotid atheroma (n = 54) were investigated with respect to (i) size and distribution of calcific deposits, (ii) indicators of chondrogenic/osteogenic transformation, and (iii) expression of fetuin-A and FGF-23. All specimens were calcified and SOX-9, collagen type II, cathepsin-K, fetuin-A and FGF-23 expression was seen in 46, 53, 53, 54 and 48 specimens, respectively. The intracellular detection of FGF-23 (45/48) indicates local synthesis. Whereas fetuin-A expression was seen also within areas of vascular smooth muscle actin-positive cells adjacent to calcific deposits, FGF-23 expression was apparently restricted to the mineralization-prone areas. Both local expression and FGF-23 serum concentrations were significantly associated with the degree of atheroma calcification. CONCLUSIONS: Besides the induction of bone islets and subsequent mineral deposition, severe remodelling of the vessel wall is sufficient to create a mineralizable fetuin-A-attracting microenvironment. FGF-23 might contribute to the formation of proper mineral, i.e. control local phosphate concentration.
Authors: Natalie A van Venrooij; Renata C Pereira; Yin Tintut; Michael C Fishbein; Navdeep Tumber; Linda L Demer; Isidro B Salusky; Katherine Wesseling-Perry Journal: Nephrol Dial Transplant Date: 2014-01-23 Impact factor: 5.992
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Authors: Dongxing Zhu; Neil C W Mackenzie; Jose Luis Millan; Colin Farquharson; Vicky E MacRae Journal: Mol Cell Endocrinol Date: 2013-03-21 Impact factor: 4.102