Expression of sarco (endo) plasmic reticulum calcium ATPase (SERCA) system in normal mouse cardiovascular tissues, heart failure and atherosclerosis.
Expression of sarco (endo) plasmic reticulum calcium ATPase (SERCA) system in normal mouse cardiovascular tissues, heart failure and atherosclerosis.
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DOI：
10.1016/j.bbamcr.2014.08.002
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发表时间：
2014-11
影响因子：
5.1
通讯作者：
Bobe, Regis
中科院分区：
文献类型：
--
作者：
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
肌浆网钙ATPase(SERCA)系统是钙循环和信号转导的关键调节因子，由多种异构体组成。我们的目的是研究SERCA亚型在小鼠心血管组织中的表达及其在心血管病理(心力衰竭和/或动脉粥样硬化)中的调节作用。在小鼠心脏和胸主动脉中检测到5种亚型(SERCA2a、2b、3a、3b和3c)。绝对信使核糖核酸定量显示SERCA2a是心脏中的主要异构体(~99%)。SERCA2和SERCA2共定位于心肌细胞(CM)纵行肌浆网(SR)，SERCA3b位于交界处。在主动脉中，SERCA2a占总SERCA的91%，SERCA2b占5%。在SERCA3中，SERCA3b的表达最高(约3.3%)，主要分布于血管平滑肌细胞(VSMC)，其次是SERCA2a和SERCA2b。在失败的CM中，SERCA2a被下调2倍，并从纵向SR重新定位到连接SR。在以合成VSMCs为主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%。综上所述：1)SERCA2a是心脏和血管细胞中的主要亚型；2)SERCA2a在心脏中的表达是血管组织的~30倍；3)SERCA2a在衰竭心肌细胞和合成VSMCs中的表达几乎是健康组织的一半，SERCA2a在衰竭心肌细胞中发生了重新定位。因此，SERCA2a是CMS和收缩VSMC兴奋-收缩偶联的主要调节因子。
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; 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.
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影响因子：
5.5
作者：
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通讯作者：
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影响因子：
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作者：
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