The level of hepatic ABCC6 expression determines the severity of calcification after cardiac injury
| العنوان: | The level of hepatic ABCC6 expression determines the severity of calcification after cardiac injury |
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| المؤلفون: | Brampton, Christopher, Aherrahrou, Zouhair, Chen, Li-Hsieh, Martin, Ludovic, Bergen, Arthur A B, Gorgels, Theo G M F, Erdmann, Jeannette, Erdfdi, Jeannette, Schunkert, Heribert, Szabó, Zalán, Váradi, András, Le Saux, Olivier |
| المساهمون: | University of Hawaii, Universität zu Lübeck [Lübeck], Biologie Neurovasculaire et Mitochondriale Intégrée (BNMI), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Netherlands Institute for Neuroscience (NIN), Royal Netherlands Academy of Arts and Sciences (KNAW), Munich Heart Alliance, German Centre for Cardiovascular Research, partner site Munich Heart Alliance, Munich, Hungarian Academy of Sciences (MTA), MUMC+: *AB Onderzoekers (9), RS: MHeNs - R3 - Neuroscience, Oogheelkunde, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université d'Angers (UA), ANS - Amsterdam Neuroscience, Human Genetics, Other departments |
| المصدر: | The American journal of pathology The American journal of pathology, 2014, 184 (1), pp.159-70. ⟨10.1016/j.ajpath.2013.09.015⟩ American Journal of Pathology, 184(1), 159-70. Elsevier Science The American journal of pathology, 184(1), 159-70. Elsevier B.V. American journal of pathology, 184(1), 159-170. Elsevier Inc. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Liver/metabolism, Pathology, medicine.medical_specialty, Heart Injury, Calcinosis/metabolism, Osteopontin/metabolism, [SDV]Life Sciences [q-bio], Blotting, Western, Myocardial Ischemia, Inbred C57BL, Real-Time Polymerase Chain Reaction, Mineralization (biology), Extracellular Matrix Proteins/metabolism, Pathology and Forensic Medicine, Mice, Calcium-Binding Proteins/metabolism, Calcinosis, Calcium-binding protein, Matrix gla protein, medicine, Animals, Humans, Osteopontin, ATP-Binding Cassette Transporters/metabolism, Multidrug Resistance-Associated Proteins/metabolism, Extracellular Matrix Proteins, biology, Blotting, Animal, Calcium-Binding Proteins, Myocardial Ischemia/metabolism/pathology, Regular Article, medicine.disease, Immunohistochemistry, Mice, Inbred C57BL, Disease Models, Animal, Heart Injuries, Liver, Heart Injuries/metabolism/pathology, Disease Models, biology.protein, Osteocalcin, ATP-Binding Cassette Transporters, Multidrug Resistance-Associated Proteins, Western, Calcification |
| الوصف: | International audience; Because vascular or cardiac mineralization is inversely correlated with morbidity and long-term survival, we investigated the role of ABCC6 in the calcification response to cardiac injury in mice. By using two models of infarction, nonischemic cryoinjury and the pathologically relevant coronary artery ligation, we confirmed a large propensity to acute cardiac mineralization in Abcc6-/- mice. Furthermore, when the expression of ABCC6 was reduced to approximately 38% of wild-type levels in Abcc6+/- mice, no calcium deposits in injured cardiac tissue were observed. In addition, we used a gene therapy approach to deliver a functional human ABCC6 via hydrodynamic tail vein injection to approximately 13% of mouse hepatocytes, significantly reducing the calcification response to cardiac cryoinjury. We observed that the level and distribution of known regulators of mineralization, such as osteopontin and matrix Gla protein, but not osteocalcin, were concomitant to the level of hepatic expression of human and mouse ABCC6. We notably found that undercarboxylated matrix Gla protein precisely colocalized within areas of mineralization, whereas osteopontin was more diffusely distributed in the area of injury, suggesting a prominent association for matrix Gla protein and osteopontin in ABCC6-related dystrophic cardiac calcification. This study showed that the expression of ABCC6 in liver is an important determinant of calcification in cardiac tissues in response to injuries and is associated with changes in the expression patterns of regulators of mineralization. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 0002-9440 1525-2191 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ddeabef7facb97665d5e4b90bc6564c8Test https://doi.org/10.1016/j.ajpath.2013.09.015Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....ddeabef7facb97665d5e4b90bc6564c8 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00029440 15252191 |
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