Department of Clinical Pharmacology, Division of Pathological Science, Kyoto Pharmaceutical University, Kyoto, 607-8414, Japan.
Nutrients. 2021 Feb 26;13(3):737. doi: 10.3390/nu13030737.
Left ventricular (LV) hypertrophy and associated heart failure are becoming a more prevalent and critical public health issue with the aging of society, and are exacerbated by reactive oxygen species (ROS). Dietary restriction (DR) markedly inhibits senescent changes; however, prolonged DR is difficult. We herein investigated whether preconditioning with short-term DR attenuates chronic pressure overload-induced cardiac hypertrophy and associated oxidative stress. Male c57BL6 mice were randomly divided into an (AL) diet or 40% restricted diet (DR preconditioning, DRPC) group for 2 weeks prior to ascending aortic constriction (AAC), and all mice were fed after AAC surgery. Two weeks after surgery, pressure overload by AAC increased LV wall thickness in association with LV diastolic dysfunction and promoted myocyte hypertrophy and cardiac fibrosis in the AL+AAC group. Oxidative stress in cardiac tissue and mitochondria also increased in the AL+AAC group in association with increments in cardiac NADPH oxidase-derived and mitochondrial ROS production. LV hypertrophy and associated cardiac dysfunction and oxidative stress were significantly attenuated in the DRPC+AAC group. Moreover, less severe mitochondrial oxidative damage in the DRPC+AAC group was associated with the suppression of mitochondrial permeability transition and cardiac apoptosis. These results indicate that chronic pressure overload-induced cardiac hypertrophy in association with cardiac and mitochondrial oxidative damage were attenuated by preconditioning with short-term DR.
左心室(LV)肥大和相关心力衰竭随着社会老龄化成为一个更为普遍和严重的公共健康问题,并且会被活性氧(ROS)所加剧。饮食限制(DR)显著抑制衰老变化;然而,长期 DR 是困难的。我们在此研究了短期 DR 预处理是否可以减轻慢性压力超负荷引起的心肌肥大和相关氧化应激。雄性 c57BL6 小鼠被随机分为正常饮食(AL)组或 40%限制饮食(DR 预处理,DRPC)组,在升主动脉缩窄(AAC)前进行 2 周预处理,所有小鼠在 AAC 手术后均喂食 。手术后 2 周,AAC 导致的压力超负荷增加了 LV 壁厚度,与 LV 舒张功能障碍有关,并促进了 AL+AAC 组的心肌细胞肥大和心脏纤维化。AL+AAC 组的心脏组织和线粒体中的氧化应激也增加,与心脏 NADPH 氧化酶衍生和线粒体 ROS 产生的增加有关。DRPC+AAC 组的 LV 肥大和相关的心脏功能障碍及氧化应激显著减轻。此外,DRPC+AAC 组的线粒体氧化损伤较轻与抑制线粒体通透性转换和心脏凋亡有关。这些结果表明,短期 DR 预处理可减轻慢性压力超负荷引起的心脏肥大以及心脏和线粒体氧化损伤。