Expression and Significance of Programmed Death-1 and Its Ligands in the Accelerated Formation of Atherosclerosis in an Induced Murine Lupus Model

Abstract

Atherosclerosis (AS) is a chronic inflammatory disease that occurs in artery walls, which seriously affects the survival and prognosis of patients with systemic lupus erythematosus (SLE). Immune and inflammatory responses have notable effects on all stages of AS. In this study, we modeled SLE combined with AS in vivo via intraperitoneal injection of pristane (2,6,10,14-tetramethylpentadecane) into apolipoprotein E-knockout (ApoE−/−) mice that had accelerated atherosclerotic lesions compared with wild-type (WT) ApoE−/− mice. In pristane-induced ApoE−/− mice, expression of programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) in peripheral blood and on the surfaces of atherosclerotic lesions significantly increased, and levels of proinflammatory cytokines, namely, interferon-gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α) in peripheral blood were elevated. We did not detect expression of programmed death-ligand 2 (PD-L2) in the arterial plaques of either pristane-induced or WT ApoE−/− mice, nor did we observe any significant difference in PD-L2 expression in peripheral blood between the two groups. Taken together, these results suggested that PD-1/PD-L1 signaling pathway might play an important regulatory role in the progression of AS in an induced murine lupus model which implies a potential target for treatment of AS in SLE.