Han Dong, Wang Chenyang, Feng Xiaojing, Hu Li, Wang Beibei, Hu Xinyue, Wu Jing
Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Biomedicines. 2024 Sep 3;12(9):2013. doi: 10.3390/biomedicines12092013.
Cardiolipin (CL), a critical phospholipid situated within the mitochondrial membrane, plays a significant role in modulating intramitochondrial processes, especially in the context of certain cardiac pathologies; however, the exact effects of alterations in cardiolipin on septic cardiomyopathy (SCM) are still debated and the underlying mechanisms remain incompletely understood. This study highlights a notable increase in the expressions of ALCAT1 and PLSCR3 during the advanced stage of lipopolysaccharide (LPS)-induced SCM. This up-regulation potential contribution to mitochondrial dysfunction and cellular apoptosis-as indicated by the augmented oxidative stress and cytochrome c (Cytc) release-coupled with reduced mitophagy, decreased levels of the antiapoptotic protein B-cell lymphoma-2 (Bcl-2) and lowered cell viability. Additionally, the timing of LPS-induced apoptosis coincides with the decline in both autophagy and mitophagy at the late stages, implying that these processes may serve as protective factors against LPS-induced SCM in HL-1 cells. Together, these findings reveal the mechanism of LPS-induced CL changes in the center of SCM, with a particular emphasis on the importance of pathological remodeling and translocation of CL to mitochondrial function and apoptosis. Additionally, it highlights the protective effect of mitophagy in the early stage of SCM. This study complements previous research on the mechanism of CL changes in mediating SCM. These findings enhance our understanding of the role of CL in cardiac pathology and provide a new direction for future research.
心磷脂（CL）是位于线粒体内膜的一种关键磷脂，在调节线粒体内过程中发挥着重要作用，尤其是在某些心脏疾病的背景下；然而，心磷脂改变对脓毒症性心肌病（SCM）的确切影响仍存在争议，其潜在机制也尚未完全阐明。本研究强调了在脂多糖（LPS）诱导的SCM晚期，ALCAT1和PLSCR3的表达显著增加。这种上调可能导致线粒体功能障碍和细胞凋亡，表现为氧化应激增强和细胞色素c（Cytc）释放增加，同时伴有线粒体自噬减少、抗凋亡蛋白B细胞淋巴瘤-2（Bcl-2）水平降低以及细胞活力下降。此外，LPS诱导的细胞凋亡时间与晚期自噬和线粒体自噬的下降相吻合，这意味着这些过程可能是HL-1细胞中对抗LPS诱导的SCM的保护因素。总之，这些发现揭示了LPS诱导的CL变化在SCM中的机制，特别强调了CL的病理重塑和易位对线粒体功能和细胞凋亡的重要性。此外，它还突出了线粒体自噬在SCM早期的保护作用。本研究补充了先前关于CL变化介导SCM机制的研究。这些发现加深了我们对CL在心脏疾病中作用的理解，并为未来的研究提供了新的方向。
