Liu Peidang, Bai Xiuying, Wang Heming, Karaplis Andrew, Goltzman David, Miao Dengshun
Department of Anatomy, Laboratory of Reproductive Medicine and The Research Center for Bone and Stem Cells, Nanjing Medical University, Nanjing, China.
Am J Physiol Heart Circ Physiol. 2009 Oct;297(4):H1514-20. doi: 10.1152/ajpheart.00581.2009. Epub 2009 Aug 14.
Fibroblast growth factor-23 (FGF-23) is a potent circulating phosphaturic factor associated with renal phosphate wasting. The effects of FGF-23 on skeletal and phosphate homeostasis have been investigated widely; however, the effect of FGF-23 on the cardiovascular system (CVS) is unknown. To assess whether FGF-23 influences the function and structure of the CVS and whether the effect of FGF-23 on the CVS is mediated by FGF receptors directly or indirectly by hypophosphatemia, FGF-23 transgenic mice and their wild-type littermates were fed a normal diet or a high-phosphate diet comprising a normal diet plus 1.25% phosphate in drinking water from weaning for 5 wk, and the phenotypes of the CVS were compared between FGF-23 transgenic mice and their wild-type littermates on the same diet. At the end of this time period, transgenic animals on the normal diet developed hypotension. The left ventricle was appropriately hypertrophic, and plasma catecholamine and renin-angiotensin system components were upregulated, indicating compensatory mechanisms in response to the hypotension. Transgenic mice also exhibited an impaired vascular reactivity and a downregulation of vasoconstrictor receptor gene expression, possibly as pathogenetic factors contributing to the hypotension. The high-phosphate diet improved the hypophosphatemia, resulting in a rescue of the cardiovascular phenotype. This study demonstrates that FGF-23 overexpression can result in abnormalities in the CVS and that the effect of FGF-23 overexpression on the CVS is mediated by the secondary severe hypophosphatemia.
成纤维细胞生长因子23（FGF - 23）是一种强效的循环磷调节因子，与肾性磷酸盐流失有关。FGF - 23对骨骼和磷酸盐稳态的影响已得到广泛研究；然而，FGF - 23对心血管系统（CVS）的影响尚不清楚。为了评估FGF - 23是否影响CVS的功能和结构，以及FGF - 23对CVS的影响是直接通过FGF受体介导还是间接通过低磷血症介导，将FGF - 23转基因小鼠及其野生型同窝小鼠从断奶开始用正常饮食或高磷饮食喂养5周，高磷饮食是在正常饮食基础上，饮水中添加1.25%的磷酸盐，然后比较相同饮食条件下FGF - 23转基因小鼠及其野生型同窝小鼠的CVS表型。在这个时间段结束时，正常饮食的转基因动物出现低血压。左心室适度肥厚，血浆儿茶酚胺和肾素 - 血管紧张素系统成分上调，表明存在对低血压的代偿机制。转基因小鼠还表现出血管反应性受损和血管收缩受体基因表达下调，这可能是导致低血压的致病因素。高磷饮食改善了低磷血症，从而挽救了心血管表型。这项研究表明，FGF - 23过表达可导致CVS异常，且FGF - 23过表达对CVS的影响是由继发性严重低磷血症介导的。
