Activation of sarcolipin expression and altered calcium cycling in LMNA cardiomyopathy
Cardiomyopathy caused by A-type lamins gene (LMNA) mutations (LMNA cardiomyopathy) is associated with dysfunction of the heart, often leading to heart failure. LMNA cardiomyopathy is highly penetrant with bad prognosis with no specific therapy available. Searching for alternative ways to halt the pr...
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doaj-76c8d36fe547439f94de9406063fe6f02020-11-25T02:36:39ZengElsevierBiochemistry and Biophysics Reports2405-58082020-07-0122Activation of sarcolipin expression and altered calcium cycling in LMNA cardiomyopathyBlanca Morales Rodriguez0Alejandro Domínguez-Rodríguez1Jean-Pierre Benitah2Florence Lefebvre3Thibaut Marais4Nathalie Mougenot5Philippe Beauverger6Gisèle Bonne7Véronique Briand8Ana-María Gómez9Antoine Muchir10Sorbonne Université, INSERM UMRS974, Paris, France; Sanofi R&D, Chilly-Mazarin, FranceInserm, Univ. Paris-Sud, Université Paris-Saclay, UMR-S 1180, “Signaling and Cardiovascular Pathophysiology”, Châtenay-Malabry, FranceInserm, Univ. Paris-Sud, Université Paris-Saclay, UMR-S 1180, “Signaling and Cardiovascular Pathophysiology”, Châtenay-Malabry, FranceInserm, Univ. Paris-Sud, Université Paris-Saclay, UMR-S 1180, “Signaling and Cardiovascular Pathophysiology”, Châtenay-Malabry, FranceSorbonne Université, INSERM UMRS974, Paris, FranceSorbonne Université, INSERM, UMS28 Phénotypage du Petit animal, Paris, F-75013, FranceSanofi R&D, Chilly-Mazarin, FranceSorbonne Université, INSERM UMRS974, Paris, FranceSanofi R&D, Chilly-Mazarin, FranceInserm, Univ. Paris-Sud, Université Paris-Saclay, UMR-S 1180, “Signaling and Cardiovascular Pathophysiology”, Châtenay-Malabry, FranceSorbonne Université, INSERM UMRS974, Paris, France; Corresponding author.Cardiomyopathy caused by A-type lamins gene (LMNA) mutations (LMNA cardiomyopathy) is associated with dysfunction of the heart, often leading to heart failure. LMNA cardiomyopathy is highly penetrant with bad prognosis with no specific therapy available. Searching for alternative ways to halt the progression of LMNA cardiomyopathy, we studied the role of calcium homeostasis in the evolution of this disease. We showed that sarcolipin, an inhibitor of the sarco/endoplasmic reticulum (SR) Ca2+ ATPase (SERCA) was abnormally elevated in the ventricular cardiomyocytes of mutated mice compared with wild type mice, leading to an alteration of calcium handling. This occurs early in the progression of the disease, when the left ventricular function was not altered. We further demonstrated that down regulation of sarcolipin using adeno-associated virus (AAV) 9-mediated RNA interference delays cardiac dysfunction in mouse model of LMNA cardiomyopathy. These results showed a novel role for sarcolipin on calcium homeostasis in heart and open perspectives for future therapeutic interventions to LMNA cardiomyopathy.http://www.sciencedirect.com/science/article/pii/S2405580820300765SarcolipinCalcium handlingNuclear envelopeLMNADilated cardiomyopathy |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Blanca Morales Rodriguez Alejandro Domínguez-Rodríguez Jean-Pierre Benitah Florence Lefebvre Thibaut Marais Nathalie Mougenot Philippe Beauverger Gisèle Bonne Véronique Briand Ana-María Gómez Antoine Muchir |
spellingShingle |
Blanca Morales Rodriguez Alejandro Domínguez-Rodríguez Jean-Pierre Benitah Florence Lefebvre Thibaut Marais Nathalie Mougenot Philippe Beauverger Gisèle Bonne Véronique Briand Ana-María Gómez Antoine Muchir Activation of sarcolipin expression and altered calcium cycling in LMNA cardiomyopathy Biochemistry and Biophysics Reports Sarcolipin Calcium handling Nuclear envelope LMNA Dilated cardiomyopathy |
author_facet |
Blanca Morales Rodriguez Alejandro Domínguez-Rodríguez Jean-Pierre Benitah Florence Lefebvre Thibaut Marais Nathalie Mougenot Philippe Beauverger Gisèle Bonne Véronique Briand Ana-María Gómez Antoine Muchir |
author_sort |
Blanca Morales Rodriguez |
title |
Activation of sarcolipin expression and altered calcium cycling in LMNA cardiomyopathy |
title_short |
Activation of sarcolipin expression and altered calcium cycling in LMNA cardiomyopathy |
title_full |
Activation of sarcolipin expression and altered calcium cycling in LMNA cardiomyopathy |
title_fullStr |
Activation of sarcolipin expression and altered calcium cycling in LMNA cardiomyopathy |
title_full_unstemmed |
Activation of sarcolipin expression and altered calcium cycling in LMNA cardiomyopathy |
title_sort |
activation of sarcolipin expression and altered calcium cycling in lmna cardiomyopathy |
publisher |
Elsevier |
series |
Biochemistry and Biophysics Reports |
issn |
2405-5808 |
publishDate |
2020-07-01 |
description |
Cardiomyopathy caused by A-type lamins gene (LMNA) mutations (LMNA cardiomyopathy) is associated with dysfunction of the heart, often leading to heart failure. LMNA cardiomyopathy is highly penetrant with bad prognosis with no specific therapy available. Searching for alternative ways to halt the progression of LMNA cardiomyopathy, we studied the role of calcium homeostasis in the evolution of this disease. We showed that sarcolipin, an inhibitor of the sarco/endoplasmic reticulum (SR) Ca2+ ATPase (SERCA) was abnormally elevated in the ventricular cardiomyocytes of mutated mice compared with wild type mice, leading to an alteration of calcium handling. This occurs early in the progression of the disease, when the left ventricular function was not altered. We further demonstrated that down regulation of sarcolipin using adeno-associated virus (AAV) 9-mediated RNA interference delays cardiac dysfunction in mouse model of LMNA cardiomyopathy. These results showed a novel role for sarcolipin on calcium homeostasis in heart and open perspectives for future therapeutic interventions to LMNA cardiomyopathy. |
topic |
Sarcolipin Calcium handling Nuclear envelope LMNA Dilated cardiomyopathy |
url |
http://www.sciencedirect.com/science/article/pii/S2405580820300765 |
work_keys_str_mv |
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