Phosphate regulation of vascular smooth muscle cell calcification.
Shuichi Jono,Marc D. McKee,Charles E. Murry,Atsushi Shioi,Yoshiki Nishizawa,Katsuhito Mori,Hirotoshi Morii,Cecilia M. Giachelli +7 more
TLDR
It is suggested that elevated phosphate may directly stimulate HSMCs to undergo phenotypic changes that predispose to calcification and offer a novel explanation of the phenomenon of vascular calcification under hyperphosphatemic conditions.Abstract:
Vascular calcification is a common finding in atherosclerosis and a serious problem in diabetic and uremic patients. Because of the correlation of hyperphosphatemia and vascular calcification, the ability of extracellular inorganic phosphate levels to regulate human aortic smooth muscle cell (HSMC) culture mineralization in vitro was examined. HSMCs cultured in media containing normal physiological levels of inorganic phosphate (1.4 mmol/L) did not mineralize. In contrast, HSMCs cultured in media containing phosphate levels comparable to those seen in hyperphosphatemic individuals (>1.4 mmol/L) showed dose-dependent increases in mineral deposition. Mechanistic studies revealed that elevated phosphate treatment of HSMCs also enhanced the expression of the osteoblastic differentiation markers osteocalcin and Cbfa-1. The effects of elevated phosphate on HSMCs were mediated by a sodium-dependent phosphate cotransporter (NPC), as indicated by the ability of the specific NPC inhibitor phosphonoformic acid, to dose dependently inhibit phosphate-induced calcium deposition as well as osteocalcin and Cbfa-1 gene expression. With the use of polymerase chain reaction and Northern blot analyses, the NPC in HSMCs was identified as Pit-1 (Glvr-1), a member of the novel type III NPCs. These data suggest that elevated phosphate may directly stimulate HSMCs to undergo phenotypic changes that predispose to calcification and offer a novel explanation of the phenomenon of vascular calcification under hyperphosphatemic conditions. The full text of this article is available at http://www.circresaha.org.read more
Citations
More filters
Journal ArticleDOI
Mineral Metabolism, Mortality, and Morbidity in Maintenance Hemodialysis
Geoffrey A. Block,Preston S. Klassen,J. Michael Lazarus,Norma J. Ofsthun,Edmund G. Lowrie,Glenn M. Chertow +5 more
TL;DR: Hyperphosphatemia and hyperparathyroidism were significantly associated with all-cause, cardiovascular, and fracture-related hospitalization, and the population attributable risk percentage for disorders of mineral metabolism was 17.5%, owing largely to the high prevalence of hyperph phosphatemia.
Journal Article
KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD)
Journal ArticleDOI
Mechanisms, Pathophysiology, and Therapy of Arterial Stiffness
TL;DR: A number of lifestyle changes and therapies that reduce arterial stiffness are presented, including weight loss, exercise, salt reduction, alcohol consumption, and neuroendocrine-directed therapies, such as those targeting the renin-angiotensin aldosterone system, natriuretic peptides, insulin modulators, as well as novel therapies that target advanced glycation end products.
Journal Article
K/DOQI clinical practice guidelines for cardiovascular disease in dialysis patients.
TL;DR: Cardiovascular Disease in Dialysis Patients Tables: An Overview of Epidemiology of Cardiovascular disease in Children and Work Group Members and Foreword.
References
More filters
Journal ArticleDOI
Transport characteristics of a murine renal Na/Pi-cotransporter.
Claudia M. Hartmann,Carsten A. Wagner,Andreas E. Busch,Daniel Markovich,Jürg Biber,Florian Lang,Heini Murer +6 more
TL;DR: The pH dependence of Na-dependent Pi transport (total Pi) may not be related primarily to a pH-dependent alteration in the availability of divalent Pi, but includes also a competitive interaction of Na with protons.
Journal ArticleDOI
Characterization of a Pi transport system in cartilage matrix vesicles. Potential role in the calcification process
TL;DR: A saturable Na(+)-dependent Pi carrier has been characterized which facilitates Pi transport in MV and its potential role for Ca-Pi accumulation into MV and subsequent development of vesicular calcification followed by mineralization of the osteogenic matrix is proposed and remains to be further investigated.
Journal ArticleDOI
Cloning and expression of a renal Na-Pi cotransport system from flounder.
TL;DR: The close functional relationship of the flounder NaPi-II protein with the previously described Na- Pi cotransport systems and the pronounced differences on the level of their primary structures provide the tools for detailed structure-function analysis of Na-Pi cotranport.
Journal ArticleDOI
Cloning of a rabbit renal Na-Pi cotransporter, which is regulated by dietary phosphate.
Tiziano Verri,Daniel Markovich,Carla Perego,Francesca Norbis,G. Stange,Victor Sorribas,Juerg Biber,Heini Murer +7 more
TL;DR: Rabbit proximal tubular BBMs contain two different Na-Pi cotransport systems: Na Pi-1 (type I) and NaPi-6 (type II).
Journal ArticleDOI
Renal sodium-phosphate cotransport
Heini Murer,J Biber +1 more
TL;DR: Molecular knowledge of proximal tubular Na/P(i) cotransport will lead to a new understanding of the cellular mechanisms of the physiologic control of proxiesimal P( i) reabsorption and to elucidation of the pathophysiologic mechanisms impairing P (i) homeostasis.