Reducing the Damage of Ox-LDL/LOX-1 Pathway to Vascular Endothelial Barrier Can Inhibit Atherosclerosis

Abstract

Aim: The destruction of the vascular endothelial barrier mediated by Ox-LDL is the initial link to atherosclerosis. Here, we aimed to determine whether the immunological intervention with Ox-ApoB polypeptide fragment (Ox-ApoB-PF) can block the deposition of Ox-LDL in vascular endothelial cells through LOX-1 receptors, thereby protecting the barrier function and survival status of vascular endothelial cells and inhibiting the progression of atherosclerosis.

Methods and results: In order to determine the harm of Ox-LDL to vascular endothelial cells and the protective effect of immune intervention with Ox-ApoB-PF, we conducted a series of corresponding experiments in vitro and in vivo. The in vitro results showed that Ox-LDL can activate endothelial cell apoptosis pathway; reduce the expression of endothelial junction proteins; affect the migration, deformation, and forming ability; and ultimately destroy the vascular endothelial barrier function. The increased permeability of endothelial cells led to a sharp increase in the phagocytosis of Ox-LDL by macrophages under the endothelial layer. Meanwhile, Ox-LDL stimulation induced a significant upregulation of LOX-1 in endothelial cells and increased the expression of endothelial cell chemokines and adhesion factors. Ox-ApoB-PF antibodies can significantly reduce the abovementioned harmful effects. The in vivo results showed that active immune intervention through Ox-ApoB-PF can protect the endothelial barrier function; reduce macrophage deposition and the inflammatory response in plaques; alleviate lipid deposition in the plaques, as well as apoptosis and necrosis; and increase the ability of liver macrophages to clear Ox-LDL. Eventually, the progression of plaque and the formation of necrotic cores in plaques can be inhibited.

Conclusions: An Ox-ApoB-PF antibody may protect the endothelial cell physiological function and survival status by blocking the combination of Ox-LDL/LOX-1 in vascular endothelial cells. Immune intervention with Ox-ApoB-PF inhibits the occurrence and development of atherosclerotic lesions by protecting the vascular endothelial barrier function.