Modulation of cardiac fibroblast function by thiazolidinediones with a focus on the role of LOX-1 / 中南大学学报(医学版)

ABSTRACT

Cardiac fibroblasts play a pivotal role in cardiac remodeling.In response to various pro-fibrotic stimuli,such as pro-inflammatory cytokines,anoxia-reoxygenation and pressure overload as well as aging,cardiac fibroblasts undergo proliferation,migration and activation,leading to the accumulation of extracellular matrix components and increased thickness and stiffness of heart.The ligands for peroxisome proliferator-activated receptor γ,especially thiazolidinediones,modulate the function of cardiac fibroblasts and the progression of cardiac remodeling,especially under pathological conditions.Unfortunately these agents have not been found to be consistently beneficial in heart failure.Although the precise intracellular signaling pathways are not fully understood,existing evidence strongly supports the involvement of oxidative stress and related signaling pathways.Further,peroxisome proliferator-activated receptor γ and lectin-like oxidized low-density lipoprotein receptor-1 together play critical roles in thiazolidinediones-modulated cardiac fibroblast dysfunction.