ROLE OF GAQ SIGNALING IN CARDIAC MYOCYTE HYPERTROPHY & APOPTOSIS

在长期超负荷的心脏中，代偿性生长 心肌通常转变为失代偿性充血 随着时间的推移心力衰竭。近年来，心肌细胞因凋亡细胞而脱落 死亡与收缩功能下降有关 在失代偿的心脏里。我们之前已经确定 G？q下游信号通路的适度激活导致 心肌细胞肥大，而这些高水平的激活 途径导致细胞凋亡。我们假设过度激活的细胞 在超负荷的心脏中G？Q介导的信号可能导致 心肌细胞的凋亡性丢失和减少的原因 在失代偿心脏中看到的收缩能力。我们建议确认 我们的体外研究结果表明，细胞凋亡是 高水平G？Q诱导心肌细胞死亡的研究 激活单个肌细胞的亚细胞结构。 收缩功能降低和细胞凋亡的早期标志物 死亡将使用电子显微镜进行评估，包括； 肌丝组织紊乱，出现胞浆 空泡，核膜和线粒体膜结构的变化。

In hearts subjected to chronic overload, compensatory growth of the myocardium commonly transitions into decompensated congestive heart failure over time. Recently, myocyte dropout by apoptotic cell death has been implicated in the decreased contractile function seen in the decompensated heart. We have previously determined that moderate activation of signaling pathways downstream of G?q cause hypertrophy in cardiac myocytes whereas high-level activation of these pathways results in apoptosis. We hypothesize that hyperactivation of G?q-mediated signaling in the overloaded heart could result in apoptotic myocyte dropout and contribute to the decreased contractility seen in the decompensated heart. We propose to confirm our in vitro findings which suggest apoptosis as the mechanism for G?q-induced myocyte death by assessing the effects of high-level G?q activation on the subcellular structures of individual myocytes. Early markers of decreased contractile function and apoptotic cell death will be evaluated using electron microscopy including; disruption of myofilament organization, appearance of cytoplasmic vaculoes, and changes in nuclear and mitochondrial membrane structure.