Evolocumab alleviates atherogenesis by inhibiting inflammation-mediated endothelial cell activation via the PI3K/AKT/NF-κB pathway.

Atherosclerosis, a chronic inflammatory disease, is the most relevant cause of ischaemic stroke or myocardial infarction. Vascular endothelial cells (ECs) play a significant role in the development of atherosclerosis. In this chronic inflammatory environment, we aimed to investigate whether a Evolocumab (Evb) could mitigate atherosclerosis progression by inhibiting EC activation via in vivo and in vitro assays. In vivo, we investigated the ability of Evb to prevent atherosclerotic lesion formation in ApoE-/- mice fed a Western diet and subjected them to carotid artery ligation. The results showed that Evb significantly inhibited the activation of carotid artery ECs to reduce the plaque area and inhibited the inflammatory response of the carotid artery. In vitro, we incubated human umbilical vein endothelial cells (HUVECs) with lipopolysaccharide (LPS). We found that the LPS-induced overexpression of VCAM-1 in HUVECs was suppressed by Evb and that the PI3K/AKT/NF-κB pathway was also suppressed by PCSK9i. We demonstrated that the level of VCAM-1 was positively correlated with that of PCSK9 in plasma and carotid plaque samples from patients with carotid artery stenosis. Moreover, we found that the protein expression levels of VCAM-1 and PCSK9 in ECs in carotid arteries with plaques were significantly greater than those in carotid arteries without plaques. Thus, the regulation of endothelial cell activation through the PI3K/AKT/NF-κB pathway may be a potential mechanism by which Evb alleviates the atherogenesis process.