Departments of Paediatrics, University of Rostock, Rostock, Germany.
Histopathology. 2010 May;56(6):775-88. doi: 10.1111/j.1365-2559.2010.03547.x.
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.
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.
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.
人类动脉粥样硬化钙化继发于血管壁的反复损伤/重塑，并且可能是由负载矿物质的胎球蛋白 A 黏附引发的，无论是否存在专业的基质矿化细胞。本研究旨在探讨成纤维细胞生长因子 (FGF)-23 对异位矿化的贡献。
对福尔马林固定石蜡包埋的人颈动脉粥样硬化（n=54）的连续切片进行了研究，以评估：(i) 钙化沉积物的大小和分布；(ii) 软骨形成/成骨转化的指标；以及 (iii) 胎球蛋白 A 和 FGF-23 的表达。所有标本均发生钙化，在 46、53、53、54 和 48 个标本中分别观察到 SOX-9、Ⅱ型胶原、组织蛋白酶 K、胎球蛋白 A 和 FGF-23 的表达。FGF-23 的细胞内检测（45/48）表明局部合成。虽然胎球蛋白 A 的表达也见于紧邻钙化沉积物的血管平滑肌肌动蛋白阳性细胞的区域内，但 FGF-23 的表达显然局限于易矿化区域。局部表达和 FGF-23 血清浓度均与动脉粥样硬化钙化程度显著相关。
除了诱导骨岛形成和随后的矿物质沉积外，血管壁的严重重塑足以产生可矿化的胎球蛋白 A 吸引微环境。FGF-23 可能有助于形成适当的矿物质，即控制局部磷酸盐浓度。
