Hcy accelerates the biological dysfunction of ANA-1 macrophages and vascular injure via Rap1A/MAPK signal

Abstract

Hyperhomocysteinemia (HHcy) is a kind of risk factor for various vascular diseases. The dysfunction of macrophages plays a crucial role in the development of HHcy-aggravated vascular injury. However, macrophages injure is still unclear. In this study, we propose the hypothesis that the Rap1A/ERK1/2 signal pathway is responsible for mediating the dysfunction of macrophages in HHcy-induced vascular diseases. We found that Cell proliferation, migration and invasion ability were increased after Hcy treatment. In addition, the mRNA levels of CD80 and CD86, and protein expression of Rap1A, iNOS were also increased in Hcy group. Interference of Rap1A reversed Hcy-induced cell proliferation, migration and invasion, and also reduced macrophage inflammatory response and M1 polarization. Phosphorylation of ERK1/2 was inhibited after Rap1A knockdown. Suppression of ERK1/2 alleviated Hcy-induced macrophage dysfunction. Together, Rap1A mediates Hcy-induced macrophage dysfunction via ERK1/2 signaling, which highlights a new mechanism in the pathogenesis and development of HHcy-aggravated vascular diseases.