Larissa Lipskaia1, Zela Keuylian2, Karl Blirando3, Nathalie Mougenot4, Adeline Jacquet4, Clotilde Rouxel3, Haifa Sghairi5, Ziane Elaib5, Regis Blaise3, Serge Adnot6, Roger J Hajjar7, Elie R Chemaly8, Isabelle Limon3, Regis Bobe9. 1. Mount Sinai School of Medicine, Cardiovascular Research Center, NY, USA; Inserm, U955, Equipe 8, Créteil, France; Université Paris-Est, Faculté de médecine, Créteil, France. 2. Sorbonne Universités, UPMC Univ Paris 06, CNRS, UMR 8256 B2A, IBPS, F-75005, Paris, France; INSERM U1155, Tenon Hospital, Paris, France. 3. Sorbonne Universités, UPMC Univ Paris 06, CNRS, UMR 8256 B2A, IBPS, F-75005, Paris, France. 4. PECMV, IFR14, Paris 6, France. 5. INSERM U770, Le Kremlin-Bicetre, France; Université Paris-sud, Le Kremlin-Bicetre, France. 6. Inserm, U955, Equipe 8, Créteil, France; Université Paris-Est, Faculté de médecine, Créteil, France. 7. Mount Sinai School of Medicine, Cardiovascular Research Center, NY, USA. 8. Mount Sinai School of Medicine, Cardiovascular Research Center, NY, USA; Department of Biomedical Engineering, University of Virginia, School of Medicine, Charlottesville, VA, USA. 9. INSERM U770, Le Kremlin-Bicetre, France; Université Paris-sud, Le Kremlin-Bicetre, France. Electronic address: regis.bobe@inserm.fr.
Abstract
UNLABELLED: The sarco(endo)plasmic reticulum Ca(2+)ATPases (SERCA) system, a key regulator of calcium cycling and signaling, is composed of several isoforms. We aimed to characterize the expression of SERCA isoforms in mouse cardiovascular tissues and their modulation in cardiovascular pathologies (heart failure and/or atherosclerosis). Five isoforms (SERCA2a, 2b, 3a, 3b and 3c) were detected in the mouse heart and thoracic aorta. Absolute mRNA quantification revealed SERCA2a as the dominant isoform in the heart (~99%). Both SERCA2 isoforms co-localized in cardiomyocytes (CM) longitudinal sarcoplasmic reticulum (SR), SERCA3b was located at the junctional SR. In the aorta, SERCA2a accounted for ~91% of total SERCA and SERCA2b for ~5%. Among SERCA3, SERCA3b was the most expressed (~3.3%), mainly found in vascular smooth muscle cells (VSMC), along with SERCA2a and 2b. In failing CM, SERCA2a was down-regulated by 2-fold and re-localized from longitudinal to junctional SR. A strong down-regulation of SERCA2a was also observed in atherosclerotic vessels containing mainly synthetic VSMCs. The proportion of both SERCA2b and SERCA3b increased to 9.5% and 8.3%, respectively. IN CONCLUSION: 1) SERCA2a is the major isoform in both cardiac and vascular myocytes; 2) the expression of SERCA2a mRNA is ~30 fold higher in the heart compared to vascular tissues; and 3) nearly half the amount of SERCA2a mRNA is measured in both failing cardiomyocytes and synthetic VSMCs compared to healthy tissues, with a relocation of SERCA2a in failing cardiomyocytes. Thus, SERCA2a is the principal regulator of excitation-contraction coupling in both CMs and contractile VSMCs.
UNLABELLED: The sarco(endo)plasmic reticulum Ca(2+)ATPases (SERCA) system, a key regulator of calcium cycling and signaling, is composed of several isoforms. We aimed to characterize the expression of SERCA isoforms in mouse cardiovascular tissues and their modulation in cardiovascular pathologies (heart failure and/or atherosclerosis). Five isoforms (SERCA2a, 2b, 3a, 3b and 3c) were detected in the mouse heart and thoracic aorta. Absolute mRNA quantification revealed SERCA2a as the dominant isoform in the heart (~99%). Both SERCA2 isoforms co-localized in cardiomyocytes (CM) longitudinal sarcoplasmic reticulum (SR), SERCA3b was located at the junctional SR. In the aorta, SERCA2a accounted for ~91% of total SERCA and SERCA2b for ~5%. Among SERCA3, SERCA3b was the most expressed (~3.3%), mainly found in vascular smooth muscle cells (VSMC), along with SERCA2a and 2b. In failing CM, SERCA2a was down-regulated by 2-fold and re-localized from longitudinal to junctional SR. A strong down-regulation of SERCA2a was also observed in atherosclerotic vessels containing mainly synthetic VSMCs. The proportion of both SERCA2b and SERCA3b increased to 9.5% and 8.3%, respectively. IN CONCLUSION: 1) SERCA2a is the major isoform in both cardiac and vascular myocytes; 2) the expression of SERCA2a mRNA is ~30 fold higher in the heart compared to vascular tissues; and 3) nearly half the amount of SERCA2a mRNA is measured in both failing cardiomyocytes and synthetic VSMCs compared to healthy tissues, with a relocation of SERCA2a in failing cardiomyocytes. Thus, SERCA2a is the principal regulator of excitation-contraction coupling in both CMs and contractile VSMCs.
Authors: L H Liu; R J Paul; R L Sutliff; M L Miller; J N Lorenz; R Y Pun; J J Duffy; T Doetschman; Y Kimura; D H MacLennan; J B Hoying; G E Shull Journal: J Biol Chem Date: 1997-11-28 Impact factor: 5.157
Authors: E Merlet; L Lipskaia; A Marchand; L Hadri; N Mougenot; F Atassi; L Liang; S N Hatem; R J Hajjar; A-M Lompré Journal: Gene Ther Date: 2012-03-29 Impact factor: 5.250
Authors: Anne-Marie Lompré; Roger J Hajjar; Sian E Harding; Evangelia G Kranias; Martin J Lohse; Andrew R Marks Journal: Circulation Date: 2010-02-01 Impact factor: 29.690
Authors: F Wuytack; B Papp; H Verboomen; L Raeymaekers; L Dode; R Bobe; J Enouf; S Bokkala; K S Authi; R Casteels Journal: J Biol Chem Date: 1994-01-14 Impact factor: 5.157
Authors: M Seth; C Sumbilla; S P Mullen; D Lewis; M G Klein; A Hussain; J Soboloff; D L Gill; G Inesi Journal: Proc Natl Acad Sci U S A Date: 2004-11-16 Impact factor: 11.205
Authors: Tengfei Bian; Joseph M Autry; Denise Casemore; Ji Li; David D Thomas; Gaohong He; Chengguo Xing Journal: Biochem Biophys Res Commun Date: 2016-11-01 Impact factor: 3.575
Authors: Jing-Yi Zhang; Gui-Bo Sun; Min Wang; Ping Liao; Yu-Yang Du; Ke Yang; Xiao-Bo Sun Journal: Toxicol Res (Camb) Date: 2016-02-08 Impact factor: 3.524
Authors: Bharathi Krishnan; Chandirasegaran Massilamany; Rakesh H Basavalingappa; Arunakumar Gangaplara; Rajkumar A Rajasekaran; Muhammad Z Afzal; Vahid Khalilzad-Sharghi; You Zhou; Jean-Jack Riethoven; Shyam S Nandi; Paras K Mishra; Raymond A Sobel; Jennifer L Strande; David Steffen; Jay Reddy Journal: J Immunol Date: 2017-12-11 Impact factor: 5.422
Authors: Chun-Chin Chen; Bo-Ruei Chen; Yinan Wang; Philip Curman; Helen A Beilinson; Ryan M Brecht; Catherine C Liu; Ryan J Farrell; Jaime de Juan-Sanz; Louis-Marie Charbonnier; Shingo Kajimura; Timothy A Ryan; David G Schatz; Talal A Chatila; Jakob D Wikstrom; Jessica K Tyler; Barry P Sleckman Journal: J Exp Med Date: 2021-05-25 Impact factor: 14.307
Authors: Isaac Jardín; José J López; Raquel Diez; José Sánchez-Collado; Carlos Cantonero; Letizia Albarrán; Geoffrey E Woodard; Pedro C Redondo; Ginés M Salido; Tarik Smani; Juan A Rosado Journal: Front Physiol Date: 2017-06-09 Impact factor: 4.566