{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T12:22:44Z","timestamp":1780921364258,"version":"3.54.1"},"reference-count":42,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,2,19]],"date-time":"2021-02-19T00:00:00Z","timestamp":1613692800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007200","name":"Medizinische Fakult\u00e4t, Ruhr-Universit\u00e4t Bochum","doi-asserted-by":"publisher","award":["K107-16"],"award-info":[{"award-number":["K107-16"]}],"id":[{"id":"10.13039\/501100007200","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Pseudoxanthoma elasticum (PXE) is an autosomal recessive disorder caused by mutations in the ATP-binding cassette sub-family C member 6 gene. Our previous studies revealed that PXE might be associated with premature aging. Treatment with statins showed positive effects not only for PXE but also for other diseases associated with premature aging like Hutchinson\u2013Gilford progeria syndrome. Nevertheless, the molecular mechanisms in the case of PXE remain unclear. Thus, this study was performed to evaluate the efficiency of atorvastatin by analyzing key characteristics of the PXE phenotype in primary human dermal fibroblasts of PXE patients. Our data indicate that an atorvastatin treatment has a positive effect, especially on factors associated with cholesterol biosynthesis and prenylation processes, whereas the effect on age- and calcification-related factors was less pronounced.<\/jats:p>","DOI":"10.3390\/cells10020442","type":"journal-article","created":{"date-parts":[[2021,2,19]],"date-time":"2021-02-19T09:06:10Z","timestamp":1613725570000},"page":"442","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Statins as a Therapeutic Approach for the Treatment of Pseudoxanthoma Elasticum Patients: Evaluation of the Spectrum Efficacy of Atorvastatin In Vitro"],"prefix":"10.3390","volume":"10","author":[{"given":"Janina","family":"Tiemann","sequence":"first","affiliation":[{"name":"Institut f\u00fcr Laboratoriums- und Transfusionsmedizin, Herz- und Diabeteszentrum Nordrhein-Westfalen, Universit\u00e4tsklinik der Ruhr-Universit\u00e4t Bochum, 32545 Bad Oeynhausen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Lindenkamp","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Laboratoriums- und Transfusionsmedizin, Herz- und Diabeteszentrum Nordrhein-Westfalen, Universit\u00e4tsklinik der Ruhr-Universit\u00e4t Bochum, 32545 Bad Oeynhausen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2265-9415","authenticated-orcid":false,"given":"Ricarda","family":"Pl\u00fcmers","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Laboratoriums- und Transfusionsmedizin, Herz- und Diabeteszentrum Nordrhein-Westfalen, Universit\u00e4tsklinik der Ruhr-Universit\u00e4t Bochum, 32545 Bad Oeynhausen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2234-9196","authenticated-orcid":false,"given":"Isabel","family":"Faust","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Laboratoriums- und Transfusionsmedizin, Herz- und Diabeteszentrum Nordrhein-Westfalen, Universit\u00e4tsklinik der Ruhr-Universit\u00e4t Bochum, 32545 Bad Oeynhausen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelius","family":"Knabbe","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Laboratoriums- und Transfusionsmedizin, Herz- und Diabeteszentrum Nordrhein-Westfalen, Universit\u00e4tsklinik der Ruhr-Universit\u00e4t Bochum, 32545 Bad Oeynhausen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3660-6923","authenticated-orcid":false,"given":"Doris","family":"Hendig","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Laboratoriums- und Transfusionsmedizin, Herz- und Diabeteszentrum Nordrhein-Westfalen, Universit\u00e4tsklinik der Ruhr-Universit\u00e4t Bochum, 32545 Bad Oeynhausen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1186\/s13023-017-0639-8","article-title":"Pseudoxanthoma Elasticum","volume":"12","author":"Germain","year":"2017","journal-title":"Orphanet. J. Rare Dis."},{"key":"ref_2","first-page":"1","article-title":"Pseudoxanthoma Elasticum","volume":"6","author":"Neldner","year":"1988","journal-title":"Clin. Derm."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.ajpath.2018.09.014","article-title":"Pseudoxanthoma Elasticum as a Paradigm of Heritable Ectopic Mineralization Disorders","volume":"189","author":"Li","year":"2019","journal-title":"Am. J. Pathol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1007\/s00795-007-0368-5","article-title":"An Autopsy Case of Pseudoxanthoma Elasticum: Histochemical Characteristics","volume":"40","author":"Miki","year":"2007","journal-title":"Med. Mol. Morphol."},{"key":"ref_5","first-page":"298","article-title":"Cardiovascular Manifestations of Pseudoxanthoma Elasticum","volume":"102","author":"Mendelsohn","year":"1978","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"4109","DOI":"10.1002\/1873-3468.13981","article-title":"From Membrane to Mineralization: The Curious Case of the ABCC6 Transporter","volume":"594","author":"Verschuere","year":"2020","journal-title":"Febs. Lett."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1016\/j.ultrasmedbio.2004.06.004","article-title":"In Patients with Pseudoxanthoma Elasticum a Thicker and More Elastic Carotid Artery Is Associated with Elastin Fragmentation and Proteoglycans Accumulation","volume":"30","author":"Kornet","year":"2004","journal-title":"Ultrasound Med. Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1390","DOI":"10.1016\/j.jvs.2011.04.041","article-title":"Relationship between Ankle Brachial Index and Arterial Remodeling in Pseudoxanthoma Elasticum","volume":"54","author":"Abraham","year":"2011","journal-title":"J. Vasc. Surg."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1038\/76102","article-title":"Mutations in a Gene Encoding an ABC Transporter Cause Pseudoxanthoma Elasticum","volume":"25","author":"Urban","year":"2000","journal-title":"Nat. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1038\/gim.2016.213","article-title":"Mutation Spectrum in the ABCC6 Gene and Genotype\u2013Phenotype Correlations in a French Cohort with Pseudoxanthoma Elasticum","volume":"19","author":"Legrand","year":"2017","journal-title":"Genet. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"20206","DOI":"10.1073\/pnas.1319582110","article-title":"ABCC6 Prevents Ectopic Mineralization Seen in Pseudoxanthoma Elasticum by Inducing Cellular Nucleotide Release","volume":"110","author":"Jansen","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1985","DOI":"10.1161\/ATVBAHA.114.304017","article-title":"ABCC6\u2013Mediated ATP Secretion by the Liver Is the Main Source of the Mineralization Inhibitor Inorganic Pyrophosphate in the Systemic Circulation\u2014Brief Report","volume":"34","author":"Jansen","year":"2014","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.jdermsci.2013.12.008","article-title":"Fibroblasts from Patients Affected by Pseudoxanthoma Elasticum Exhibit an Altered PPi Metabolism and Are More Responsive to Pro-Calcifying Stimuli","volume":"74","author":"Boraldi","year":"2014","journal-title":"J. Derm. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1038\/jid.2012.460","article-title":"Matrix Gla Protein and Alkaline Phosphatase Are Differently Modulated in Human Dermal Fibroblasts from PXE Patients and Controls","volume":"133","author":"Boraldi","year":"2013","journal-title":"J. Investig. Dermatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1007\/s00246-010-9711-z","article-title":"Aortic Calcification in a Patient with Hutchinson\u2013Gilford Progeria Syndrome","volume":"31","author":"Salamat","year":"2010","journal-title":"Pediatr. Cardiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.arr.2016.06.007","article-title":"Hutchinson-Gilford Progeria Syndrome: A Premature Aging Disease Caused by LMNA Gene Mutations","volume":"33","author":"Gonzalo","year":"2017","journal-title":"Ageing Res. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"536","DOI":"10.14336\/AD.2019.0610","article-title":"Cellular and Molecular Biomarkers Indicate Premature Aging in Pseudoxanthoma Elasticum Patients","volume":"11","author":"Tiemann","year":"2020","journal-title":"Aging Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2442","DOI":"10.1161\/CIRCULATIONAHA.112.000571","article-title":"Defective Extracellular Pyrophosphate Metabolism Promotes Vascular Calcification in a Mouse Model of Hutchinson-Gilford Progeria Syndrome That Is Ameliorated on Pyrophosphate Treatment","volume":"127","author":"Osorio","year":"2013","journal-title":"Circulation"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1007\/s00109-013-1066-5","article-title":"Atorvastatin counteracts Aberrant Soft Tissue Mineralization in a Mouse Model of Pseudoxanthoma Elasticum (Abcc6\u2212\/\u2212)","volume":"91","author":"Guo","year":"2013","journal-title":"J. Mol. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1007\/s00109-013-1082-5","article-title":"Pseudoxanthoma Elasticum and Statin Prophylaxis","volume":"91","author":"Luft","year":"2013","journal-title":"J. Mol. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1126\/science.1059344","article-title":"Structural Mechanism for Statin Inhibition of HMG-CoA Reductase","volume":"292","author":"Istvan","year":"2001","journal-title":"Science"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/S0021-9150(00)00397-X","article-title":"Statins and Cardiovascular Diseases: The Multiple Effects of Lipid-Lowering Therapy by Statins","volume":"153","author":"Rauch","year":"2000","journal-title":"Atherosclerosis"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.molmed.2007.11.004","article-title":"Pleiotropic Effects of Statin Therapy: Molecular Mechanisms and Clinical Results","volume":"14","author":"Wang","year":"2008","journal-title":"Trends Mol. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1210\/en.2002-220682","article-title":"Statins Augment Vascular Endothelial Growth Factor Expression in Osteoblastic Cells via Inhibition of Protein Prenylation","volume":"144","author":"Maeda","year":"2003","journal-title":"Endocrinology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1186\/1476-511X-13-118","article-title":"ABCC6- a New Player in Cellular Cholesterol and Lipoprotein Metabolism?","volume":"13","author":"Kuzaj","year":"2014","journal-title":"Lipids Health Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/S0022-2275(20)43173-6","article-title":"3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Activity in Cultured Fibroblasts from Patients with Mevalonate Kinase Deficiency: Differential Response to Lipid Supplied by Fetal Bovine Serum in Tissue Culture Medium","volume":"31","author":"Gibson","year":"1990","journal-title":"J. Lipid Res."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Lau, W.M., Doucet, M., Stadel, R., Huang, D., Weber, K.L., and Kominsky, S.L. (2013). Enpp1: A Potential Facilitator of Breast Cancer Bone Metastasis. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0066752"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1038\/343425a0","article-title":"Regulation of the Mevalonate Pathway","volume":"343","author":"Goldstein","year":"1990","journal-title":"Nature"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"12131","DOI":"10.1016\/S0021-9258(19)49815-3","article-title":"Cloning and Expression of a Cellular High Density Lipoprotein-Binding Protein That Is up-Regulated by Cholesterol Loading of Cells","volume":"267","author":"McKnight","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2350","DOI":"10.1161\/01.ATV.17.11.2350","article-title":"High-Density Lipoprotein-Binding Protein (HBP)\/Vigilin Is Expressed in Human Atherosclerotic Lesions and Colocalizes With Apolipoprotein E","volume":"17","author":"Chiu","year":"1997","journal-title":"ATVB"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e2824","DOI":"10.1038\/cddis.2017.221","article-title":"HMG-CoA Reductase Promotes Protein Prenylation and Therefore Is Indispensible for T-Cell Survival","volume":"8","author":"Lacher","year":"2017","journal-title":"Cell Death Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1592\/phco.26.3.333","article-title":"Modulatory Effects of AT on Endothelial Cell-Derived Chemokines, Cytokines, and Angiogenic Factors","volume":"26","author":"Zineh","year":"2006","journal-title":"Pharmacotherapy"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1742-4933-4-1","article-title":"The Interleukin-6 Inflammation Pathway from Cholesterol to Aging--Role of Statins, Bisphosphonates and Plant Polyphenols in Aging and Age-Related Diseases","volume":"4","author":"Omoigui","year":"2007","journal-title":"Immun. Ageing"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1530\/EJE-12-0844","article-title":"AT Administration Is Associated with Dose-Related Changes in IGF Bioavailability","volume":"168","author":"Narayanan","year":"2013","journal-title":"Eur. J. Endocrinol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"5455","DOI":"10.1210\/en.2005-0714","article-title":"The Local Expression and Abundance of Insulin-like Growth Factor (IGF) Binding Proteins in Skeletal Muscle Are Regulated by Age and Gender but Not Local IGF-I in Vivo","volume":"146","author":"Oliver","year":"2005","journal-title":"Endocrinology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1926","DOI":"10.1038\/mt.2016.160","article-title":"GDF11 Protects against Endothelial Injury and Reduces Atherosclerotic Lesion Formation in Apolipoprotein E-Null Mice","volume":"24","author":"Mei","year":"2016","journal-title":"Mol. Ther."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.jdermsci.2014.04.015","article-title":"Pyrophosphates as a Major Inhibitor of Matrix Calcification in Pseudoxanthoma Elasticum","volume":"75","author":"Kuzaj","year":"2014","journal-title":"J. Derm. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"39059","DOI":"10.1074\/jbc.M111.221689","article-title":"Ectonucleotide Pyrophosphatase\/Phosphodiesterase-1 (ENPP1) Protein Regulates Osteoblast Differentiation","volume":"286","author":"Nam","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1038\/195911a0","article-title":"Mechanism of Calcification: Inhibitory Role of Pyrophosphate","volume":"195","author":"Fleisch","year":"1962","journal-title":"Nature"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1038\/ki.2013.521","article-title":"Vascular Calcification Is Dependent on Plasma Levels of Pyrophosphate","volume":"85","author":"Lomashvili","year":"2014","journal-title":"Kidney Int."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/S0169-6009(08)80225-5","article-title":"Osteopontin-Hydroxyapatite Interactions in Vitro: Inhibition of Hydroxyapatite Formation and Growth in a Gelatin-Gel","volume":"22","author":"Boskey","year":"1993","journal-title":"Bone Min."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1016\/S0945-053X(00)00108-6","article-title":"Osteopontin: A Versatile Regulator of Inflammation and Biomineralization","volume":"19","author":"Giachelli","year":"2000","journal-title":"Matrix Biol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/2\/442\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:26:17Z","timestamp":1760160377000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/2\/442"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,19]]},"references-count":42,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021,2]]}},"alternative-id":["cells10020442"],"URL":"https:\/\/doi.org\/10.3390\/cells10020442","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,19]]}}}