Donate-Correa Javier, Martín-Núñez Ernesto, Hernández-Carballo Carolina, Ferri Carla, Tagua Víctor G, Delgado-Molinos Alejandro, López-Castillo Ángel, Rodríguez-Ramos Sergio, Cerro-López Purificación, López-Tarruella Victoria Castro, Felipe-García Raquel, Arévalo-Gomez Miguel A, Pérez-Delgado Nayra, Mora-Fernández Carmen, Navarro-González Juan F
Research Unit, University Hospital Nuestra Señora de Candelaria (UHNSC), Santa Cruz de Tenerife, Spain.
Doctoral and Graduate School, University of La Laguna, San Cristóbal de La Laguna, Tenerife, Spain.
Aging (Albany NY). 2019 Sep 22;11(18):7899-7913. doi: 10.18632/aging.102297.
Vascular calcification is a major risk for cardiovascular disease and implies the transformation of smooth muscle cells to an osteoblastic phenotype as a consequence of dysregulation of calcium and phosphate metabolism. Fibroblast growth factor (FGF) 23 is the most potent phosphate regulator. Observational studies suggest that high levels of FGF23 are related to cardiovascular morbidity and mortality. In this work, we determined the levels of both the intact and the carboxi-terminal fragments of circulating FGF23 in 133 patients with established cardiovascular disease, the expression of FGF23, its receptors 1 and 3, and its co-receptor Klotho in vascular fragments of aorta, carotid and femoral in 43 out of this group of patients, and in a control group of 20 organ donors. Patients with atherosclerosis and vascular calcification presented increased levels of FGF23 respect to the control group. Vascular immunoreactivity for FGF23 was also significantly increased in patients with vascular calcification as compared to patients without calcification and to controls. Finally, gene expression of and were also higher and directly related in vascular samples with calcification. Conversely, expression of was reduced in patients with cardiovascular disease when comparing to controls. In conclusion, our findings link the calcification of the vascular tissue with the expression of FGF23 in the vessels and with the elevation of circulating levels this hormone.
血管钙化是心血管疾病的主要风险因素,意味着由于钙和磷代谢失调,平滑肌细胞向成骨细胞表型转变。成纤维细胞生长因子(FGF)23是最有效的磷酸盐调节因子。观察性研究表明,高水平的FGF23与心血管疾病的发病率和死亡率相关。在这项研究中,我们测定了133例已确诊心血管疾病患者循环中完整FGF23和羧基末端片段的水平,在该组43例患者以及20例器官捐献者对照组的主动脉、颈动脉和股动脉血管片段中FGF23及其受体1和3以及共受体Klotho的表达。与对照组相比,患有动脉粥样硬化和血管钙化的患者FGF23水平升高。与无钙化患者和对照组相比,血管钙化患者FGF23的血管免疫反应性也显著增加。最后,在有钙化的血管样本中,FGF23及其受体的基因表达也更高且直接相关。相反,与对照组相比,心血管疾病患者中Klotho的表达降低。总之,我们的研究结果将血管组织的钙化与血管中FGF23的表达以及该激素循环水平的升高联系起来。