Is the enhancement of the sarcoplasmic reticulum function susceptible to arrhythmias?

肌浆网功能增强是否易发生心律失常？

• 批准号: 13670748
• 负责人: MINAMISAWA Susumu
• 金额: $ 2.62万
• 依托单位: Yokohama City University (2002)Tokyo Women's Medical University (2001)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670748/
• 关键词: Heart Failure; calcium cycling; arrhythmias; sarcoplasmic reticulum; electrophysiology; phospholamban

Calcium is not only indispensable for normal muscle contraction and relaxation but also an important second messenger of various signaling pathways in the heart. A growing body of evidence has shown that Ca^<2+> homeostasis and Ca^<2+> -dependent signaling pathways play a pivotal role in the development of cardiac hyperirophy and heart failure. The enhancement of Ca^<2+> uptake via cardiac SR Ca^<2+> ATPase (SERCA2a) may have potential therapeutic value for heart failure. Arrhythmogenesis is a potential adverse effect of the enhancement of Ca^<2+> uptake. To establish the safety of this treatment, we examined the susceptibility of arrhythmias in phospholamban knockout mice which display the almost maximal SERCA2a activity. The programmed electrophysiological study and telemetry electrocardiography revealed that phospholamban ablation was not susceptible to arrhythmias in mice. The data indicated that phospholamban ablation could be a novel therapeutic strategy for heart failure without the potent risk of arrhythmogenesis.

钙不仅是正常肌肉收缩和舒张所不可缺少的，而且是心脏各种信号通路的重要第二信使。越来越多的证据表明，Ca^2+稳态和Ca^2+依赖性信号通路在心肌肥厚和心力衰竭的发生发展中起着关键作用。心肌肌浆网Ca ^2 + ATP酶（SERCA 2a）介导的Ca^2+摄取增加可能对心力衰竭具有潜在的治疗价值。心律失常发生是Ca^2+摄取增强的一个潜在的不利影响。为了确定这种治疗的安全性，我们检查了受磷蛋白基因敲除小鼠中心律失常的易感性，这些小鼠显示出几乎最大的SERCA2a活性。程序电生理研究和遥测心电图显示受磷蛋白消融对小鼠心律失常不敏感。这些数据表明受磷蛋白消融可能是心力衰竭的一种新的治疗策略，而没有潜在的心脏病风险。

项目成果

Minamisawa S, Wang Y, Chen J, Ishikawa Y, Chien KR, Matsuoka R.: "Atrial-chainber specific expression of sarcolipin is regulated during development and hypertrophic remodling"J Biol Chem. 278(11). 9570-9575 (2003)

Minamisawa S、Wang Y、Chen J、Ishikawa Y、Chien KR、Matsuoka R.：“肌磷脂的心房链特异性表达在发育和肥大重塑过程中受到调节”J Biol Chem。

Minamisawa S, Sato Y, Tasuguchi Y, Fujino T, Imamura S, Uetsuka Y, Nakazawa M, Matsuoka R.: "Mutation of the phospholanbam promoter associated with hypertrophic cardiomyopathy"Biochem Biophys Res Commun. 304(1). 1-4 (2003)

Minamisawa S、Sato Y、Tasuguchi Y、Fujino T、Imamura S、Uetsuka Y、Nakazawa M、Matsuoka R.：“与肥厚型心肌病相关的磷兰巴姆启动子的突变”Biochem Biophys Res Commun。

Minamisawa S, et al.: "Atrial-chamber specific expression of sarcolipin is regulated during development and hypertrophic remodeling"J Biol Chem. 278. 9570-9575 (2003)

Minamisawa S 等人：“肌磷脂的心房特异性表达在发育和肥大重塑过程中受到调节”J Biol Chem。

Minamisawa S., et al.: "Mutation of the phospholanbam promoter associated with hypertrophic cardiomyopathy"Biochem Biophys Res Commun. 304. 1-4 (2003)

Minamisawa S.等人：“与肥厚型心肌病相关的磷蛋白启动子的突变”Biochem Biophys Res Commun。