Expression of sarco (endo) plasmic reticulum calcium ATPase (SERCA) system in normal mouse cardiovascular tissues, heart failure and atherosclerosis

Larissa Lipskaia, Zela Keuylian, Karl Blirando, Nathalie Mougenot, Adeline Jacquet, Clotilde Rouxel, Haifa Sghairi, Ziane Elaib, Regis Blaise, Serge Adnot, Roger J. Hajjar, Elie R. Chemaly, Isabelle Limon, Regis Bobe

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44 Scopus citations

Abstract

The sarco(endo)plasmic reticulum Ca2+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.

Original languageEnglish
Pages (from-to)2705-2718
Number of pages14
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1843
Issue number11
DOIs
StatePublished - Nov 2014

Keywords

  • Calcium signaling
  • Cardiovascular
  • Heart
  • SERCA
  • Smooth muscle cells

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