PKD knockdown mitigates Ang II-induced cardiac hypertrophy and ferroptosis via the JNK/P53 signaling pathway.
PKD knockdown mitigates Ang II-induced cardiac hypertrophy and ferroptosis via the JNK/P53 signaling pathway.
复制标题
DOI：
10.1016/j.cellsig.2023.110974
复制
发表时间：
2023-11
影响因子：
4.8
通讯作者：
Chanyuan Lv;Liuyi Zhou;Yongkang Meng;Haitao Yuan;Jing Geng
中科院分区：
文献类型：
--
作者：
Chanyuan Lv;Liuyi Zhou;Yongkang Meng;Haitao Yuan;Jing Geng
研究背景心肌肥厚与能量代谢、自噬和铁凋亡的关系，这些与心血管不良事件和慢性心力衰竭有关。蛋白激酶D（PKD）已被证明在心脏肥大中发挥退行性作用。然而，在PKD涉及的心肌hypertrophy的作用仍不清楚。MethodsA心肌肥厚模型是通过皮下注射血管紧张素II（Ang II）4周。在注射Ang II之前2周通过尾静脉注射腺相关病毒血清型9（AAV 9）-PKD或AAV 9-阴性对照。通过超声心动图和心肌细胞形态学观察评估心肌肥厚程度。在体内和体外测定Jun N-末端激酶（JNK）/P53信号通路中的铁凋亡和蛋白表达水平。结果表明，PKD敲低降低Ang II诱导的心肌肥大，增强心功能，抑制铁凋亡。体内和体外实验进一步证实了JNK/P53通路参与了这一过程。结论总之，我们的研究结果表明PKD敲低通过JNK/P53信号通路减轻了Ang II诱导的心脏肥大和铁细胞凋亡。
BackgroundCardiac hypertrophy is studied in relation to energy metabolism, autophagy, and ferroptosis, which are associated with cardiovascular adverse events and chronic heart failure. Protein kinase D (PKD) has been shown to play a degenerative role in cardiac hypertrophy. However, the role of ferroptosis in PKD-involved cardiac hypertrophy remains unclear.MethodsA cardiac hypertrophy model was induced by a subcutaneous injection of angiotensin II (Ang II) for 4 weeks. Adeno-associated virus serotype 9 (AAV9)-PKD or AAV9-Negative control were injected through the caudal vein 2 weeks prior to the injection of Ang II. The degree of cardiac hypertrophy was assessed using echocardiography and by observing cardiomyocyte morphology. Levels of ferroptosis and protein expression in the Jun N-terminal kinase (JNK)/P53 signaling pathway were measured bothin vivoandin vitro.ResultsThe results indicated that PKD knockdown reduces Ang II-induced cardiac hypertrophy, enhances cardiac function and inhibits ferroptosis. The involvement of the JNK/P53 pathway in this process was further confirmed byin vivoandin vitroexperiments.ConclusionIn conclusion, our findings suggest that PKD knockdown mitigates Ang II-induced cardiac hypertrophy and ferroptosisviathe JNK/P53 signaling pathway.