Cardiac memory is associated with decreased levels of the transcriptional factor CREB modulated by angiotensin II and calcium
Cardiac memory is associated with decreased levels of the transcriptional factor CREB modulated by angiotensin II and calcium
复制标题
DOI：
10.1161/01.res.0000088785.24381.2f
复制
发表时间：
2003-09-05
影响因子：
20.1
通讯作者：
Rosen, MR
中科院分区：
文献类型：
--
作者：
Patberg, KW;Plotnikov, AN;Rosen, MR
心脏记忆（CM）有短期（STCM）和长期（LTCM）的钙和血管紧张素II调制的成分。LTCM与I-to和Kv4.3 mRNA水平降低相关。由于cAMP反应元件结合蛋白，CREB，有助于中枢神经系统的记忆转录，我们假设它可能是一个转录因子在CM，钙和血管紧张素II的影响。我们研究了STCM的狗，AV顺序起搏（AVP）2小时或假手术。用ECG和心电向量图（VCG）评估STCM，并在5至120分钟时进行心外膜下活检，并研究CREB。在起搏3周的犬和假手术对照组中研究了LTCM。在3周时，切除心脏，获得活组织检查，并测试CRE结合。STCM诱导发生在AVP犬中，但不发生在假手术或用萨拉新或硝苯地平治疗的AVP犬中。仅AVP未用药组在2 h时核CREB显著降低。LTCM狗表现出减少核蛋白结合CRE，和CRE结合活性的启动子区Kv4.3。总之，STCM诱导和核CREB减少之间存在关联，这是血管紧张素调节和钙依赖性的。此外，AVP 3周后CRE结合的降低与Kv4.3启动子中的CRE结合活性相结合可以解释作为LTCM特征的Kv4.3 mRNA和I-to下调。
Cardiac memory (CM) has short- (STCM) and long-term (LTCM) components modulated by calcium and angiotensin II. LTCM is associated with reduced I-to and Kv4.3 mRNA levels. Because the cAMP response element binding protein, CREB, contributes to CNS memory transcription, we hypothesized that it might be a transcriptional factor in CM, influenced by calcium and angiotensin II. We studied STCM in dogs that were AV sequentially paced (AVP) for 2 hours or sham-operated. STCM was evaluated with ECG and vectorcardiogram (VCG), and subepicardial biopsies were taken at 5 to 120 minutes and investigated for CREB. LTCM was studied in dogs paced for 3 weeks and in sham controls. At 3 weeks the heart was excised, biopsies obtained, and CRE binding tested. STCM induction occurred in AVP dogs but not in sham or AVP dogs treated with saralasin or nifedipine. Nuclear CREB was significantly decreased at 2 hours in the AVP no-drug group only. LTCM dogs manifested reduced binding of nuclear proteins to CRE, and CRE binding activity in the promoter region of Kv4.3. In conclusion, there is an association between STCM induction and decreased nuclear CREB that is angiotensin-modulated and calcium-dependent. Moreover, the decreased CRE binding after 3 weeks of AVP combined with CRE binding activity in the Kv4.3 promoter can explain the Kv4.3 mRNA and I-to downregulation that characterize LTCM.