Phenotypic Modulation of Cultured Primary Human Aortic Vascular Smooth Muscle Cells by Uremic Serum

Frontiers in Physiology

José R. López-López¹  M. Teresa Pérez-García¹  Pilar Cidad¹  Teresa Giraldez²  Diego Alvarez de la Rosa²  Ernesto Martín-Núñez³  Violeta Cazaña-Pérez³  Juan F. Navarro-González³  Javier Donate-Correa³ 

[1] Departamento de Bioquímica y Biología Molecular y Fisiología e Instituto de Biología y Genética Molecular (IBGM), Universidad de Valladolid y Consejo Superior de Investigaciones Científicas (CSIC), Valladolid, Spain;Departamento de Ciencias Médicas Básicas (Fisiología), Instituto de Tecnologías Biomédicas and Centro de Investigaciones Biomédicas de Canarias, Universidad de La Laguna, Tenerife, Spain;Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, Tenerife, Spain;

关键词: vascular calcification;    uremia;    chronic kidney disease;    apoptosis;    osteogenic differentiation;    uremic serum;   

DOI  :  10.3389/fphys.2018.00089

来源: DOAJ

【 摘 要 】

Patients with chronic kidney disease (CKD) have a markedly increased incidence of cardiovascular disease (CVD). The high concentration of circulating uremic toxins and alterations in mineral metabolism and hormone levels produce vascular wall remodeling and significant vascular damage. Medial calcification is an early vascular event in CKD patients and is associated to apoptosis or necrosis and trans-differentiation of vascular smooth muscle cells (VSMC) to an osteogenic phenotype. VSMC obtained from bovine or rat aorta and cultured in the presence of increased inorganic phosphate (Pi) have been extensively used to study these processes. In this study we used human aortic VSMC primary cultures to compare the effects of increased Pi to treatment with serum obtained from uremic patients. Uremic serum induced calcification, trans-differentiation and phenotypic remodeling even with normal Pi levels. In spite of similar calcification kinetics, there were fundamental differences in osteochondrogenic marker expression and alkaline phosphatase induction between Pi and uremic serum-treated cells. Moreover, high Pi induced a dramatic decrease in cell viability, while uremic serum preserved it. In summary, our data suggests that primary cultures of human VSMC treated with serum from uremic patients provides a more informative model for the study of vascular calcification secondary to CKD.

【 授权许可】

Unknown