Jeremic Nevena, Weber Gregory J, Tyagi Suresh C
Health Sciences Centre, Department of Physiology, School of Medicine, University of Louisville, 500 South Preston Street, Louisville, KY 40202, USA.
Can J Physiol Pharmacol. 2017 Nov;95(11):1369-1375. doi: 10.1139/cjpp-2016-0744. Epub 2017 Jul 24.
Hyperhomocysteinemia (HHcy) is a risk factor for adverse cardiovascular events; however, the mechanism for development of this disease is still unknown. Toll-like receptor 4 (TRL4) is a molecule involved in the immune response pathway and is quickly becoming a receptor of interest in the field of hypertension. In this study, we hypothesized that ablation of TLR4 mitigates cardiac mitochondrial dysfunction in a model of HHcy. Five strains of mice (C57BL/6J, CBS, C3H, CBS/C3H, and C3H/HeOuJ) 10-12 weeks old were utilized. We found that HHcy causes heart hypertrophy and promotes oxidative stress while mice with HHcy and inactivated TLR4 showed significant improvement in examined parameters. A dominance of endothelial cell mitochondrial fission over mitochondrial fusion in HHcy and oxidative stress was observed, which may explain the endothelial cell loss and dysfunction that contributes to inward cardiac remodeling.
高同型半胱氨酸血症（HHcy）是心血管不良事件的一个风险因素；然而，这种疾病的发病机制仍不清楚。Toll样受体4（TRL4）是一种参与免疫反应途径的分子，并且正迅速成为高血压领域中一个受关注的受体。在本研究中，我们假设在HHcy模型中，TLR4的缺失可减轻心脏线粒体功能障碍。使用了5株10 - 12周龄的小鼠（C57BL/6J、CBS、C3H、CBS/C3H和C3H/HeOuJ）。我们发现HHcy会导致心脏肥大并促进氧化应激，而HHcy且TLR4失活的小鼠在所检测的参数上显示出显著改善。在HHcy和氧化应激中观察到内皮细胞线粒体裂变超过线粒体融合占主导地位，这可能解释了导致心脏内向重塑的内皮细胞丢失和功能障碍。
