ROLE OF GAQ SIGNALING IN CARDIAC MYOCYTE HYPERTROPHY & APOPTOSIS

在慢性超负荷的心脏中， 心肌通常会转变为失代偿充血性 随着时间的推移心力衰竭。 近年来，凋亡细胞导致的心肌细胞脱落 死亡与收缩功能下降有关 在失代偿的心脏中。 我们之前已经确定， 中度激活信号通路下游的G？q原因 心肌细胞肥大，而高水平激活这些 途径导致细胞凋亡。 我们假设， G吗？超负荷心脏中的q介导信号可能导致 凋亡的心肌细胞脱落，并有助于减少 失代偿心脏的收缩力 我们建议确认 我们的体外研究结果表明，细胞凋亡是 G吗？q诱导的心肌细胞死亡的影响，评估高水平G？Q 激活单个肌细胞的亚细胞结构。 收缩功能下降和凋亡细胞的早期标志物 将使用电子显微镜评价死亡，包括; 肌丝组织破坏，出现细胞质 空泡，核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.