Cellular distribution of Ca2+ pumps and Ca2+ release channels in rat cardiac hypertrophy induced by aortic stenosis
Cellular distribution of Ca2+ pumps and Ca2+ release channels in rat cardiac hypertrophy induced by aortic stenosis
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DOI：
10.1161/01.cir.98.22.2477
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发表时间：
1998-12-01
期刊：
影响因子：
37.8
通讯作者：
Samuel, JL
中科院分区：
文献类型：
--
作者：
Anger, M;Lompré, AM;Samuel, JL
背景：心室肌细胞对压力过载的反应是异质性的，而且不是空间协调的。我们研究了心肌中SERCA和RyR基因表达的改变是否均匀。方法和结果：采用原位杂交和免疫荧光技术分别分析了2个sarco（内do）质网Ca2+- atp酶（SERCA）亚型（SERCA 2a和2b）和2个Ca2+释放通道（ryanodine受体RyR和IP3受体IP3R）的mrna和蛋白的细胞分布。对胸主动脉狭窄（AS）致大鼠心肌肥厚的早期（1天和5天）和晚期（1个月）进行分析。结果表明，AS后1天和5天，右心室和心房的SERCA 2a和RyR2 mRNA的细胞分布与对照组相似，但左心室部分区域的mRNA水平出现下降。AS后1个月，SERCA 2a mRNA和蛋白在整个左室的分布呈异质性，而RyR2 mRNA和蛋白水平呈均匀性下降。SERCA 2b在对照组心肌细胞和血管中均表达不良，AS发生后1个月仅在冠状动脉中增加4倍。在sham （Sh）和AS中，主要在血管中发现SERCA 3和IP3R mrna。结论：在严重肥厚中，SERCA 2a积累的减少是不均匀的，并且不能通过诱导心肌细胞中的SERCA 2b来补偿。RyR2表达的减少更为均匀，并且不会被IP3R表达的增加所补偿。
Background-The response of ventricular myocytes to pressure overload is heterogeneous and not spatially coordinated. We investigated whether or not the alterations in SERCA and RyR gene expression are homogeneous within the myocardium.Methods and Results-The cellular distribution of mRNAs and proteins encoding the 2 sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) isoforms (SERCA 2a and 2b) and 2 Ca2+ release channels (the ryanodine receptor, RyR, and the IP3 receptor, IP3R) were analyzed by in situ hybridization and immunofluorescence, respectively. Analyses were performed during early (1 and 5 days) and late (1 month) stages of cardiac hypertrophy induced in rat by thoracic aortic stenosis (AS). The results indicated that 1 and 5 days after AS, the cellular distribution of SERCA 2a and RyR2 mRNAs in right ventricle and atrium was similar to controls but the mRNA levels appeared to decrease in some areas of the left ventricle (LV). One month after AS, the distribution of SERCA 2a mRNA and protein became heterogeneous throughout the LV, whereas RyR2 mRNA and protein levels were decreased in a homogeneous manner. SERCA 2b, poorly expressed in both cardiomyocytes and vessels of controls, was increased 4-fold 1 month after AS in coronary arteries only. In both sham (Sh) and AS, SERCA 3 and IP3R mRNAs were mainly found in the vessels.Conclusions-In severe hypertrophy, decreased accumulation of SERCA 2a was heterogeneous and not compensated by an induction of SERCA 2b in the cardiomyocytes. Decrease in RyR2 expression was more homogeneous and not compensated by an increased IP3R expression.