Lipskaia Larissa, Keuylian Zela, Blirando Karl, Mougenot Nathalie, Jacquet Adeline, Rouxel Clotilde, Sghairi Haifa, Elaib Ziane, Blaise Regis, Adnot Serge, Hajjar Roger J, Chemaly Elie R, Limon Isabelle, Bobe Regis
Mount Sinai School of Medicine, Cardiovascular Research Center, NY, USA; Inserm, U955, Equipe 8, Créteil, France; Université Paris-Est, Faculté de médecine, Créteil, France.
Sorbonne Universités, UPMC Univ Paris 06, CNRS, UMR 8256 B2A, IBPS, F-75005, Paris, France; INSERM U1155, Tenon Hospital, Paris, France.
Biochim Biophys Acta. 2014 Nov;1843(11):2705-18. doi: 10.1016/j.bbamcr.2014.08.002. Epub 2014 Aug 7.
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.
肌浆（内质）网Ca²⁺ATP酶（SERCA）系统是钙循环和信号传导的关键调节因子，由多种亚型组成。我们旨在表征SERCA亚型在小鼠心血管组织中的表达及其在心血管疾病（心力衰竭和/或动脉粥样硬化）中的调节情况。在小鼠心脏和胸主动脉中检测到五种亚型（SERCA2a、2b、3a、3b和3c）。绝对mRNA定量显示SERCA2a是心脏中的主要亚型（约99%）。两种SERCA2亚型共定位于心肌细胞（CM）的纵行肌浆网（SR），SERCA3b位于连接肌浆网。在主动脉中，SERCA2a占总SERCA的约91%，SERCA2b占约5%。在SERCA3中，SERCA3b表达最多（约3.3%），主要存在于血管平滑肌细胞（VSMC）中，同时还有SERCA2a和2b。在衰竭的心肌细胞中，SERCA2a下调2倍，并从纵行肌浆网重新定位于连接肌浆网。在主要含有合成型VSMC的动脉粥样硬化血管中也观察到SERCA2a的强烈下调。SERCA2b和SERCA3b的比例分别增加到9.5%和8.3%。
1）SERCA2a是心脏和血管肌细胞中的主要亚型；2）与血管组织相比，心脏中SERCA2a mRNA的表达高约30倍；3）与健康组织相比，衰竭心肌细胞和合成型VSMC中SERCA2a mRNA的量几乎减少一半，且SERCA2a在衰竭心肌细胞中重新定位。因此，SERCA2a是心肌细胞和收缩性VSMC中兴奋 - 收缩偶联的主要调节因子。
