Ablation of toll-like receptor 4 mitigates cardiac mitochondrial dysfunction in hyperhomocysteinemia.

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.