Endogenous Calcification Inhibitors in the Prevention of Vascular Calcification: A Consensus Statement From the COST Action EuroSoftCalcNet

Frontiers in Cardiovascular Medicine

卷:5

Catherine Shanahan¹  Victor Sorribas²  Flora Szeri³  Pedro Valdivielso⁴  Olivier Vanakker⁵  Hervé Kempf⁶  Andreas Pasch⁷  M. Leonor Cancela⁸  Natércia Conceição⁸  Frank Rutsch⁹  Yvonne Nitschke⁹  Daniela Quaglino¹⁰  Georges Leftheriotis¹¹  Ludovic Martin¹²  Tamas Aranyi¹³  Vicky Macrae¹⁴  Miguel Carracedo¹⁵  Magnus Bäck¹⁵ 

[1] 0British Heart Foundation Centre of Research Excellence, James Black Centre, School of Cardiovascular Medicine and Sciences, King's College London, London, United Kingdom;

[2] 1Laboratory of Molecular Toxicology, Veterinary Faculty, University of Zaragoza, Zaragoza, Spain;

[3] 2Department of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, United States;

[4] 3Internal Medicine, Instituto de Investigación Biomédica (IBIMA), Virgen de la Victoria University Hospital, Universidad de Málaga, Málaga, Spain;

[5] 4Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium;

[6] 5UMR 7365 CNRS-Université de Lorraine, IMoPA, Vandoeuvre-lès-Nancy, France;

[7] Calciscon AG, Nidau, Switzerland;

[8] Department of Biomedical Sciences and Medicine, Algarve Biomedical Centre, Centre of Marine Sciences/CCMAR, University of Algarve, Faro, Portugal;

[9] Department of General Pediatrics, Münster University Children's Hospital, Münster, Germany;

[10] Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy;

[11] LP2M, University of Nice-Sophia Antipolis and Vascular Physiology and Medicine, University Hospital of Nice, Nice, France;

[12] PXE Reference Center, Angers University Hospital, Angers, France;

[13] Research Center for Natural Sciences, Institute of Enzymology, Hungarian Academy of Sciences, Budapest, Hungary;

[14] The Roslin Institute and Royal School of Veterinary Studies, University of Edinburgh, Edinburgh, United Kingdom;

[15] Translational Cardiology, Center for Molecular Medicine, Karolinska University Hospital Stockholmt, Stockholm, Sweden;

关键词: arterial calcification;    pyrophosphate;    gla proteins;    klotho;    osteoprotegerin;    osteopontin;   

DOI  :  10.3389/fcvm.2018.00196

来源: DOAJ

【 摘 要 】

The physicochemical deposition of calcium-phosphate in the arterial wall is prevented by calcification inhibitors. Studies in cohorts of patients with rare genetic diseases have shed light on the consequences of loss-of-function mutations for different calcification inhibitors, and genetic targeting of these pathways in mice have generated a clearer picture on the mechanisms involved. For example, generalized arterial calcification of infancy (GACI) is caused by mutations in the enzyme ecto-nucleotide pyrophosphatase/phosphodiesterase-1 (eNPP1), preventing the hydrolysis of ATP into pyrophosphate (PPi). The importance of PPi for inhibiting arterial calcification has been reinforced by the protective effects of PPi in various mouse models displaying ectopic calcifications. Besides PPi, Matrix Gla Protein (MGP) has been shown to be another potent calcification inhibitor as Keutel patients carrying a mutation in the encoding gene or Mgp-deficient mice develop spontaneous calcification of the arterial media. Whereas PPi and MGP represent locally produced calcification inhibitors, also systemic factors contribute to protection against arterial calcification. One such example is Fetuin-A, which is mainly produced in the liver and which forms calciprotein particles (CPPs), inhibiting growth of calcium-phosphate crystals in the blood and thereby preventing their soft tissue deposition. Other calcification inhibitors with potential importance for arterial calcification include osteoprotegerin, osteopontin, and klotho. The aim of the present review is to outline the latest insights into how different calcification inhibitors prevent arterial calcification both under physiological conditions and in the case of disturbed calcium-phosphate balance, and to provide a consensus statement on their potential therapeutic role for arterial calcification.

【 授权许可】

Unknown