title: Expression of sarco (endo) plasmic reticulum calcium ATPase (SERCA) system in normal mouse cardiovascular tissues, heart failure and atherosclerosis.
abstract: 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.
  
  
  CONCLUSIONS
  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.affiliation: Mount Sinai School of Medicine, Cardiovascular Research Center, NY, USA; Inserm, U955, Equipe 8, Créteil, France; Université Paris-Est, Faculté de médecine, Créteil, France.
authors.forename: Larissa
authors.initials: L
authors.lastname: Lipskaia
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, CNRS, UMR 8256 B2A, IBPS, F-75005, Paris, France; INSERM U1155, Tenon Hospital, Paris, France.
authors.forename: Zela
authors.initials: Z
authors.lastname: Keuylian
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, CNRS, UMR 8256 B2A, IBPS, F-75005, Paris, France.
authors.forename: Karl
authors.initials: K
authors.lastname: Blirando
authors.affiliation: PECMV, IFR14, Paris 6, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Mougenot
authors.affiliation: PECMV, IFR14, Paris 6, France.
authors.forename: Adeline
authors.initials: A
authors.lastname: Jacquet
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, CNRS, UMR 8256 B2A, IBPS, F-75005, Paris, France.
authors.forename: Clotilde
authors.initials: C
authors.lastname: Rouxel
authors.affiliation: INSERM U770, Le Kremlin-Bicetre, France; Université Paris-sud, Le Kremlin-Bicetre, France.
authors.forename: Haifa
authors.initials: H
authors.lastname: Sghairi
authors.affiliation: INSERM U770, Le Kremlin-Bicetre, France; Université Paris-sud, Le Kremlin-Bicetre, France.
authors.forename: Ziane
authors.initials: Z
authors.lastname: Elaib
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, CNRS, UMR 8256 B2A, IBPS, F-75005, Paris, France.
authors.forename: Regis
authors.initials: R
authors.lastname: Blaise
authors.affiliation: Inserm, U955, Equipe 8, Créteil, France; Université Paris-Est, Faculté de médecine, Créteil, France.
authors.forename: Serge
authors.initials: S
authors.lastname: Adnot
authors.affiliation: Mount Sinai School of Medicine, Cardiovascular Research Center, NY, USA.
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Hajjar
authors.affiliation: Mount Sinai School of Medicine, Cardiovascular Research Center, NY, USA; Department of Biomedical Engineering, University of Virginia, School of Medicine, Charlottesville, VA, USA.
authors.forename: Elie R
authors.initials: ER
authors.lastname: Chemaly
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, CNRS, UMR 8256 B2A, IBPS, F-75005, Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Limon
authors.affiliation: INSERM U770, Le Kremlin-Bicetre, France; Université Paris-sud, Le Kremlin-Bicetre, France. Electronic address: regis.bobe@inserm.fr.
authors.forename: Regis
authors.initials: R
authors.lastname: Bobe
keywords: Ca(2)(+)ATPase; Calcium signaling; Cardiovascular; Heart; SERCA; Smooth muscle cells
references.citation: Circ Res. 2005 Sep 2;97(5):488-95
references.pmid: 16081870
references.citation: J Biol Chem. 1994 Jan 14;269(2):1410-6
references.pmid: 8288608
references.citation: Biochem Biophys Res Commun. 2006 Jul 14;345(4):1377-85
references.pmid: 16725111
references.citation: Circulation. 2010 Feb 16;121(6):822-30
references.pmid: 20124124
references.citation: Cell Calcium. 2009 Feb;45(2):144-54
references.pmid: 18947868
references.citation: J Clin Invest. 2013 Jan;123(1):46-52
references.pmid: 23281409
references.citation: Circ Res. 2001 Oct 26;89(9):838-46
references.pmid: 11679415
references.citation: Physiology (Bethesda). 2007 Oct;22:328-34
references.pmid: 17928546
references.citation: Curr Vasc Pharmacol. 2013 Jul;11(4):465-79
references.pmid: 23905641
references.citation: Muscle Nerve. 2007 Apr;35(4):430-42
references.pmid: 17286271
references.citation: Mol Ther. 2010 Jul;18(7):1284-92
references.pmid: 20461063
references.citation: J Biol Chem. 1993 Apr 15;268(11):8325-31
references.pmid: 7681842
references.citation: J Biol Chem. 2004 Jun 4;279(23):24297-306
references.pmid: 15028735
references.citation: J Biol Chem. 2003 Mar 28;278(13):11359-68
references.pmid: 12524443
references.citation: Circ Res. 2003 May 30;92(10):1115-22
references.pmid: 12730091
references.citation: Biochem J. 2006 Apr 15;395(2):249-58
references.pmid: 16402920
references.citation: Cell Calcium. 2003 Dec;34(6):457-64
references.pmid: 14572804
references.citation: Ann N Y Acad Sci. 2012 Apr;1254:42-50
references.pmid: 22548568
references.citation: J Biol Chem. 2002 Jul 5;277(27):24442-52
references.pmid: 11956212
references.citation: J Physiol. 2002 Dec 1;545(2):615-27
references.pmid: 12456838
references.citation: J Biol Chem. 1992 Jul 15;267(20):14483-9
references.pmid: 1385815
references.citation: Cell Calcium. 2007 Sep;42(3):281-9
references.pmid: 17306367
references.citation: J Mol Cell Cardiol. 2001 Jun;33(6):1283-95
references.pmid: 11444930
references.citation: Hypertension. 2000 Jan;35(1 Pt 1):91-102
references.pmid: 10642281
references.citation: Biochem J. 2001 Sep 15;358(Pt 3):559-68
references.pmid: 11535119
references.citation: J Mol Cell Cardiol. 2011 Apr;50(4):621-33
references.pmid: 21195084
references.citation: Biochem J. 1992 Sep 1;286 ( Pt 2):591-5
references.pmid: 1326945
references.citation: Hypertension. 2001 Jan;37(1):135-141
references.pmid: 11208768
references.citation: Expert Opin Biol Ther. 2010 Jan;10(1):29-41
references.pmid: 20078230
references.citation: Exp Cell Res. 1999 Aug 1;250(2):364-75
references.pmid: 10413590
references.citation: Cardiovasc Res. 2008 Jan 15;77(2):315-24
references.pmid: 18006436
references.citation: Am J Physiol Heart Circ Physiol. 2014 Jan 1;306(1):H88-100
references.pmid: 24186100
references.citation: J Physiol. 2002 Apr 1;540(Pt 1):219-29
references.pmid: 11927681
references.citation: Gene Ther. 2013 Mar;20(3):248-54
references.pmid: 22456325
references.citation: Arterioscler Thromb Vasc Biol. 2000 May;20(5):1225-35
references.pmid: 10807737
references.citation: Methods. 2001 Dec;25(4):402-8
references.pmid: 11846609
references.citation: Proc Natl Acad Sci U S A. 2004 Nov 23;101(47):16683-8
references.pmid: 15546997
references.citation: Am J Physiol. 1999 Aug;277(2):L264-70
references.pmid: 10444520
references.citation: Aviat Space Environ Med. 2002 Jul;73(7):635-9
references.pmid: 12137098
references.citation: J Biol Chem. 1997 Nov 28;272(48):30538-45
references.pmid: 9374548
references.citation: Nature. 2002 Jan 10;415(6868):198-205
references.pmid: 11805843
references.citation: Curr Drug Targets. 2008 Mar;9(3):251-60
references.pmid: 18336244
references.citation: J Biol Chem. 2000 Aug 11;275(32):24722-7
references.pmid: 10816568
references.citation: J Vasc Res. 2000 Nov-Dec;37(6):568-75
references.pmid: 11146411
references.citation: Gene Ther. 2013 Apr;20(4):396-406
references.pmid: 22763406
references.citation: J Mol Cell Cardiol. 2010 Apr;48(4):633-44
references.pmid: 19962989