Up-regulation of AT1 and AT2 receptors in postinfarcted hypertrophied myocytes and stretch-mediated apoptotic cell death
Up-regulation of AT1 and AT2 receptors in postinfarcted hypertrophied myocytes and stretch-mediated apoptotic cell death
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DOI：
10.1016/s0002-9440(10)65037-7
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发表时间：
2000-05-01
影响因子：
6
通讯作者：
Anversa, P
中科院分区：
文献类型：
--
作者：
Leri, A;Liu, Y;Anversa, P
为了确定AT(1)和AT(2)受体的上调是否发生在梗死后肥厚的肌细胞中，以及AT(2)是否在拉伸介导的细胞凋亡中发挥作用，我们在冠状动脉闭塞和心力衰竭后8天将大鼠左心室肌细胞与残存的壁分离。对照细胞取自假手术动物。在等双轴拉伸装置中拉伸肌细胞，测量血管紧张素II （Ang II）的形成和细胞死亡。12小时后。AT(1)和AT(2)蛋白在刚分离的肌细胞和拉伸后进行测定。我们还证实了AT(1)和AT(2)拮抗剂对拉伸诱导的Ang II合成和细胞凋亡的影响。心肌梗死增加了肌细胞AT(1)和AT(2)，拉伸进一步上调了这些受体。在梗死后的肌细胞中，Ang II水平较高，并且在两组细胞中，这种肽随着拉伸时间的延长而增加。同样，对照组和梗死后心肌细胞凋亡随时间增加。在拉伸后3和12小时，心肌细胞中Ang II和凋亡的绝对值更大。在培养物中添加AT(1)阻滞剂可抑制拉伸激活的心肌细胞凋亡以及梗死后心肌细胞中Ang II的生成。相比之下，AT(2)拮抗剂对这些细胞事件没有影响。综上所述，Ang II通过AT(1)受体激活刺激细胞死亡，而与AT(2)受体结合的配体不改变正常和梗死后肥大肌细胞的Ang II浓度和凋亡。
To determine whether up-regulation of AT(1) and AT(2) receptors occurred in hypertrophied myocytes after infarction and whether AT(2) played a role in stretch-mediated apoptosis, left ventricular myocytes were dissociated from the surviving portion of the wall 8 days after coronary occlusion and cardiac failure in rats. Control cells were obtained from sham-operated animals. Myocytes were stretched in an equibiaxial stretch apparatus and angiotensin II (Ang II) formation and cell death were measured 3 and. 12 hours later. AT(1) and AT(2) proteins were evaluated in freshly isolated myocytes and after stretch. The effects of AT(1) and AT(2) antagonists on stretch-induced Ang II synthesis and apoptosis were also established. Myocardial infarction increased AT(1) and AT(2) in myocytes and stretch further up-regulated these receptors. Ang II levels were higher in postinfarcted myocytes and this peptide increased with the duration of stretch in both groups of cells. Similarly, apoptosis increased with time in control and postinfarcted myocytes. Absolute values of Ang II and apoptosis were greater in myocytes from infarcted hearts at 3 and 12 hours after stretch. Addition of AT(1) blocker to cultures Inhibited stretch-activated apoptosis in both myocyte populations as well as the generation of Ang II in postinfarcted myocytes. In contrast, AT(2) antagonists had no impact on these cellular events. In conclusion, Ang II stimulated cell death through AT(1) receptor activation, whereas Ligand binding to AT(2) receptor did not alter Ang II concentration and apoptosis in normal and postinfarcted hypertrophied myocytes.