Hydroxysafflor yellow A-loaded biomimetic liposomes alleviate HHcy-induced atherosclerosis by regulating methylation related autophagy

Abstract

Cardiovascular disease (CVD) caused by atherosclerosis has become a main threaten for human health. As an independent risk factor, hyperhomocysteinemia (HHcy) played an important role in the pathogenesis of atherosclerosis by regulating DNA methylation modification and autophagy of macrophages. In this study, we constructed a new kind of macro-liposome nanoparticle by hybridizing liposome with macrophages membranes (Møm) to encapsulate hydroxysafflower yellow A (HSYA). Assertion of Hyaluronic acid (HA) on the macro-liposome NPs was adopted to endow nanodrug targeting ability. In vitro results showed that the prepared macro-liposome nanoparticles can significantly inhibit Atg13 DNA methylation, while enhance autophagy of macrophages to promote cholesterol efflux, as well. In vivo studies have shown that the HA modification made the macro-liposome NPs an ideal decoy for targeting plaques. Thus, the macro-liposome NPs with prolonged blood circulation time, and improved targeting ability can achieve optimal HSYA accumulation at the region of atherosclerotic plaques to obtain high efficacy. According to our point, the nano-drug delivery system with high immune escape capability provided a feasible therapeutic strategy for efficient atherosclerosis therapy.

Keywords

• Atherosclerosis
• Hyperhomocysteinemia
• Hydroxylsafflower yellow A
• Atg13 DNA methylation
• Autophagy