Chih-Yu Yang1, Zee-Fen Chang2, Yat-Pang Chau3, Ann Chen4, Wu-Chang Yang5, An-Hang Yang6, Oscar Kuang-Sheng Lee7. 1. Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan School of Medicine, National Yang-Ming University, Taipei, Taiwan Division of Nephrology, Taipei Veterans General Hospital, Taipei, Taiwan. 2. Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan. 3. Department of Medicine, Mackay Medical College, New Taipei City, Taiwan. 4. Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan. 5. School of Medicine, National Yang-Ming University, Taipei, Taiwan Division of Nephrology, Taipei Veterans General Hospital, Taipei, Taiwan. 6. Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan School of Medicine, National Yang-Ming University, Taipei, Taiwan Department of Pathology, Taipei Veterans General Hospital, Taipei, Taiwan. 7. Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan School of Medicine, National Yang-Ming University, Taipei, Taiwan Stem Cell Research Center, National Yang-Ming University, Taipei, Taiwan Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan Department of Orthopedic Surgery, Taipei City Hospital, Taipei, Taiwan.
Abstract
BACKGROUND: The process of vascular calcification has been associated with the canonical Wnt/β-catenin signalling pathway in cell cultures and animal studies. The relationship between circulating Wnt/β-catenin inhibitors and vascular calcification in dialysis patients is unknown. The aim of this study was to investigate the associations between serum dickkopf-1 (Dkk-1) and sclerostin, two circulating inhibitors of the Wnt/β-catenin signalling pathway, and the severity of aortic calcification (AoC) and cardiovascular outcomes in dialysis patients. METHODS: This was a prospective observational cohort study. One hundred and twenty-five patients on maintenance haemodialysis participated in the study. Serum levels of Dkk-1 and sclerostin were measured. AoC scores were calculated from plain films of both posterior-anterior and lateral views. The patients were followed up for 2 years or until death or withdrawal. RESULTS: The circulating sclerostin level was inversely associated with the severity of AoC (P = 0.035) and indicators of the bone turnover rate including serum alkaline phosphatase (ALP) (r = -0.235, P = 0.008) and intact parathyroid hormone (r = -0.523, P < 0.001). Furthermore, Cox regression analysis indicated that the patients with high circulating sclerostin levels were less likely to experience future cardiovascular events [1 pmol/L sclerostin increase, hazard ratio 0.982 (95% CI, 0.967-0.996), P = 0.015] after adjusting for a propensity score. In contrast, serum Dkk-1 was not associated with AoC and clinical outcomes. CONCLUSIONS: In long-term haemodialysis patients, circulating sclerostin but not Dkk-1 is inversely associated with AoCs and future cardiovascular events. Our findings suggest that sclerostin, as a bone-related protein, might act as a communicator between uraemic bone and vasculature.
BACKGROUND: The process of vascular calcification has been associated with the canonical Wnt/β-catenin signalling pathway in cell cultures and animal studies. The relationship between circulating Wnt/β-catenin inhibitors and vascular calcification in dialysis patients is unknown. The aim of this study was to investigate the associations between serum dickkopf-1 (Dkk-1) and sclerostin, two circulating inhibitors of the Wnt/β-catenin signalling pathway, and the severity of aortic calcification (AoC) and cardiovascular outcomes in dialysis patients. METHODS: This was a prospective observational cohort study. One hundred and twenty-five patients on maintenance haemodialysis participated in the study. Serum levels of Dkk-1 and sclerostin were measured. AoC scores were calculated from plain films of both posterior-anterior and lateral views. The patients were followed up for 2 years or until death or withdrawal. RESULTS: The circulating sclerostin level was inversely associated with the severity of AoC (P = 0.035) and indicators of the bone turnover rate including serum alkaline phosphatase (ALP) (r = -0.235, P = 0.008) and intact parathyroid hormone (r = -0.523, P < 0.001). Furthermore, Cox regression analysis indicated that the patients with high circulating sclerostin levels were less likely to experience future cardiovascular events [1 pmol/L sclerostin increase, hazard ratio 0.982 (95% CI, 0.967-0.996), P = 0.015] after adjusting for a propensity score. In contrast, serum Dkk-1 was not associated with AoC and clinical outcomes. CONCLUSIONS: In long-term haemodialysis patients, circulating sclerostin but not Dkk-1 is inversely associated with AoCs and future cardiovascular events. Our findings suggest that sclerostin, as a bone-related protein, might act as a communicator between uraemic bone and vasculature.
Authors: Wilhelmina A Touw; Thor Ueland; Jens Bollerslev; John T Schousboe; Wai H Lim; Germaine Wong; Peter L Thompson; Douglas P Kiel; Richard L Prince; Fernando Rivadeneira; Joshua R Lewis Journal: J Endocr Soc Date: 2017-01-12
Authors: Cristina Novo-Rodríguez; Beatriz García-Fontana; Juan De Dios Luna-Del Castillo; Francisco Andújar-Vera; Verónica Ávila-Rubio; Cristina García-Fontana; Sonia Morales-Santana; Pedro Rozas-Moreno; Manuel Muñoz-Torres Journal: PLoS One Date: 2018-06-21 Impact factor: 3.240