Apigenin Attenuates Atherogenesis through Inducing Macrophage Apoptosis via Inhibition of AKT Ser473 Phosphorylation and Downregulation of Plasminogen Activator Inhibitor-2

Abstract EN

Macrophage survival is believed to be a contributing factor in the development of early atherosclerotic lesions.

Dysregulated apoptosis of macrophages is involved in the inflammatory process of atherogenesis.

Apigenin is a flavonoid that possesses various clinically relevant properties such as anti-inflammatory, antiplatelet, and antitumor activities.

Here we showed that apigenin attenuated atherogenesis in apo E - / - mice in an in vivo test.

In vitro experiments suggested that apigenin induced apoptosis of oxidized low density lipoprotein- (OxLDL-) loaded murine peritoneal macrophages (MPMs).

Proteomic analysis showed that apigenin reduced the expression of plasminogen activator inhibitor 2 (PAI-2).

PAI-2 has antiapoptotic effects in OxLDL-loaded MPMs.

Enhancing PAI-2 expression significantly reduced the proapoptosis effects of apigenin.

Molecular docking assay with AutoDock software predicted that residue Ser473 of Akt1 is a potential binding site for apigenin.

Lentiviral-mediated overexpression of Akt1 wild type weakened the proapoptosis effect of apigenin in OxLDL-loaded MPMs.

Collectively, apigenin executes its anti-atherogenic effects through inducing OxLDL-loaded MPMs apoptosis.

The proapoptotic effects of apigenin were at least partly attributed to downregulation of PAI-2 through suppressing phosphorylation of AKT at Ser473.