Horvath Orsolya, Ordog Katalin, Bruszt Kitti, Kalman Nikoletta, Kovacs Dominika, Radnai Balazs, Gallyas Ferenc, Toth Kalman, Halmosi Robert, Deres Laszlo
1st Department of Medicine, University of Pecs, Medical School, Pecs, Hungary.
Szentágothai Research Centre, University of Pecs, Pecs, Hungary.
Oxid Med Cell Longev. 2021 Feb 27;2021:6643871. doi: 10.1155/2021/6643871. eCollection 2021.
Heart failure (HF) is a complex chronic clinical disease characterized by among others the damage of the mitochondrial network. The disruption of the mitochondrial quality control and the imbalance in fusion-fission processes lead to a lack of energy supply and, finally, to cell death. BGP-15 (O-[3-piperidino-2-hydroxy-1-propyl]-nicotinic acid amidoxime dihydrochloride) is an insulin sensitizer molecule and has a cytoprotective effect in a wide variety of experimental models. In our recent work, we aimed to clarify the mitochondrial protective effects of BGP-15 in a hypertension-induced heart failure model and "in vitro." Spontaneously hypertensive rats (SHRs) received BGP-15 or placebo for 18 weeks. BGP-15 treatment preserved the normal mitochondrial ultrastructure and enhanced the mitochondrial fusion. Neonatal rat cardiomyocytes (NRCMs) were stressed by hydrogen-peroxide. BGP-15 treatment inhibited the mitochondrial fission processes, promoted mitochondrial fusion, maintained the integrity of the mitochondrial genome, and moreover enhanced the de novo biogenesis of the mitochondria. As a result of these effects, BGP-15 treatment also supports the maintenance of mitochondrial function through the preservation of the mitochondrial structure during hydrogen peroxide-induced oxidative stress as well as in an "in vivo" heart failure model. It offers the possibility, which pharmacological modulation of mitochondrial quality control under oxidative stress could be a novel therapeutic approach in heart failure.
心力衰竭（HF）是一种复杂的慢性临床疾病，其特征包括线粒体网络受损等。线粒体质量控制的破坏以及融合-裂变过程的失衡导致能量供应不足，最终导致细胞死亡。BGP-15（O-[3-哌啶基-2-羟基-1-丙基]-烟酰胺肟二盐酸盐）是一种胰岛素增敏剂分子，在多种实验模型中具有细胞保护作用。在我们最近的工作中，我们旨在阐明BGP-15在高血压诱导的心力衰竭模型和“体外”模型中的线粒体保护作用。自发性高血压大鼠（SHRs）接受BGP-15或安慰剂治疗18周。BGP-15治疗可保留正常的线粒体超微结构并增强线粒体融合。新生大鼠心肌细胞（NRCMs）受到过氧化氢的应激。BGP-15治疗可抑制线粒体裂变过程，促进线粒体融合，维持线粒体基因组的完整性，此外还可增强线粒体的从头生物合成。由于这些作用，BGP-15治疗还通过在过氧化氢诱导的氧化应激期间以及在“体内”心力衰竭模型中保留线粒体结构来支持线粒体功能的维持。它提供了一种可能性，即在氧化应激下对线粒体质量控制进行药理学调节可能是心力衰竭的一种新型治疗方法。
