Ana María Sánchez-Tévar1, María García-Fernández2, Belén Murcia-Casas3, José Rioja-Villodres1,4, Juan Luis Carrillo3, Marta Camacho5, Matthias Van Gils6,7, Miguel Angel Sánchez-Chaparro1,3,4, Olivier Vanakker6,7, Pedro Valdivielso1,3,4. 1. Lipid and Arteriosclerosis Laboratory, Centro de Investigaciones Médico-Sanitarias (CIMES), University of Málaga, Málaga, Spain. 2. Department of Physiology, Instituto de Investigación Biomédica de Málaga (IBIMA), University of Málaga, Málaga, Spain. 3. Internal Medicine Unit, Hospital Virgen de la Victoria, Málaga, Spain. 4. Department of Medicine and Dermatology, Instituto de Investigación Biomédica de Málaga (IBIMA), University of Málaga, Málaga, Spain. 5. Obstetric and Gynecology Department, Hospital Virgen de la Victoria, Málaga, Spain. 6. Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium. 7. Department of Biomolecular Medicine, Ghent University, Ghent, Belgium.
Abstract
BACKGROUND: Inorganic pyrophosphate (PPi) plays a major role inhibiting dystrophic calcification. The aim was to analyze levels of PPi in patients having pseudoxanthoma elasticum (PXE), and controls as well as the enzymes who regulate the PPi plasma concentration. METHODS: We collected fasting blood samples from PXE patients and age- and sex-matched controls in ethylenediamine tetraacetic acid (EDTA) and citrate-theophylline-adenosine-dipyridamole (CTAD) containing tubes. We measured PPi, ENPP1 mass and activity, alkaline phosphatase (AP) and tissue non-specific alkaline phosphatase (TNAP), CD73 and Human Platelet Factor-4 (CXCL4). RESULTS: PPi in EDTA and CTAD samples were lower in PXE subjects than in controls (1.11±0.26 vs. 1.43±0.41 µM/L and 0.35±0.15 vs. 0.61±0.18 µM/L respectively, P<0.05). TNAP and liver TNAP activities were also higher in PXE than in controls (80.3±27.0 vs. 63.3±16.4 UI/L and 25.6±14.9 vs. 12.9±9.2 UI/L respectively, P<0.05). ENPP1 mass and activity as well as CD73 were almost identical. There was a weak but significant inverse correlation between TNAP activity and PPi levels (Pearson correlation -0.379, P<0.05) in both groups. CONCLUSIONS: High TNAP activity seems to contribute to low plasma levels of PPi in subjects with PXE, reinforcing the idea that pharmacological reduction of TNAP activity may help to reduce dystrophic calcification in PXE patients. 2019 Annals of Translational Medicine. All rights reserved.
BACKGROUND: Inorganic pyrophosphate (PPi) plays a major role inhibiting dystrophic calcification. The aim was to analyze levels of PPi in patients having pseudoxanthoma elasticum (PXE), and controls as well as the enzymes who regulate the PPi plasma concentration. METHODS: We collected fasting blood samples from PXE patients and age- and sex-matched controls in ethylenediamine tetraacetic acid (EDTA) and citrate-theophylline-adenosine-dipyridamole (CTAD) containing tubes. We measured PPi, ENPP1 mass and activity, alkaline phosphatase (AP) and tissue non-specific alkaline phosphatase (TNAP), CD73 and Human Platelet Factor-4 (CXCL4). RESULTS: PPi in EDTA and CTAD samples were lower in PXE subjects than in controls (1.11±0.26 vs. 1.43±0.41 µM/L and 0.35±0.15 vs. 0.61±0.18 µM/L respectively, P<0.05). TNAP and liver TNAP activities were also higher in PXE than in controls (80.3±27.0 vs. 63.3±16.4 UI/L and 25.6±14.9 vs. 12.9±9.2 UI/L respectively, P<0.05). ENPP1 mass and activity as well as CD73 were almost identical. There was a weak but significant inverse correlation between TNAP activity and PPi levels (Pearson correlation -0.379, P<0.05) in both groups. CONCLUSIONS: High TNAP activity seems to contribute to low plasma levels of PPi in subjects with PXE, reinforcing the idea that pharmacological reduction of TNAP activity may help to reduce dystrophic calcification in PXE patients. 2019 Annals of Translational Medicine. All rights reserved.
Authors: Astrid S Plomp; Johan Toonstra; Arthur A B Bergen; Marijke R van Dijk; Paulus T V M de Jong Journal: Am J Med Genet A Date: 2010-04 Impact factor: 2.802
Authors: Shira G Ziegler; Carlos R Ferreira; Elena Gallo MacFarlane; Ryan C Riddle; Ryan E Tomlinson; Emily Y Chew; Ludovic Martin; Chen-Ting Ma; Eduard Sergienko; Anthony B Pinkerton; José Luis Millán; William A Gahl; Harry C Dietz Journal: Sci Transl Med Date: 2017-06-07 Impact factor: 17.956
Authors: Magnus Bäck; Tamas Aranyi; M Leonor Cancela; Miguel Carracedo; Natércia Conceição; Georges Leftheriotis; Vicky Macrae; Ludovic Martin; Yvonne Nitschke; Andreas Pasch; Daniela Quaglino; Frank Rutsch; Catherine Shanahan; Victor Sorribas; Flora Szeri; Pedro Valdivielso; Olivier Vanakker; Hervé Kempf Journal: Front Cardiovasc Med Date: 2019-01-18
Authors: Lukas Nollet; Matthias Van Gils; Suzanne Fischer; Laurence Campens; Swapna Karthik; Andreas Pasch; Julie De Zaeytijd; Bart P Leroy; Daniel Devos; Tine De Backer; Paul J Coucke; Olivier M Vanakker Journal: J Clin Med Date: 2022-06-28 Impact factor: 4.964
Authors: Nathan D Maulding; Dillon Kavanagh; Kristin Zimmerman; Gianfilippo Coppola; Thomas O Carpenter; Nathaniel K Jue; Demetrios T Braddock Journal: Bone Date: 2020-09-24 Impact factor: 4.398
Authors: Antonio Gutierrez-Cardo; Eugenia Lillo; Belén Murcia-Casas; Juan Luis Carrillo-Linares; Francisco García-Argüello; Purificación Sánchez-Sánchez; Alejandro Rodriguez-Morata; Isabel Baquero Aranda; Miguel Ángel Sánchez-Chaparro; María García-Fernández; Pedro Valdivielso Journal: J Clin Med Date: 2020-05-08 Impact factor: 4.241