Anti-β2GPI antibodies enhance atherosclerosis in ApoE-deficient mice

Abstract Accelerated atherosclerosis often occurs in patients with antiphospholipid syndrome (APS), and auto-antibodies to β 2 glycoprotein I (anti-β 2 GPI) are confirmed as pathogenic antibodies to APS. Our previous studies have demonstrated that the conversion of mouse peritoneal macrophages into foam cells could be enhanced by co-existence of β 2 GPI and anti-β 2 GPI IgG, but this phenomenon has not been explored in vivo . Here, we present a mouse model to observe the effect of anti-β 2 GPI IgG in the development of atherosclerosis. Male ApoE-deficient mice were intraperitoneally injected with anti-β 2 GPI IgG (100 μg/mouse) and homologous control IgG (100 μg/mouse) every week for 16 weeks. Plasma lipid composition, magnetic resonance imaging (MRI) and histological staining were used to evaluate vascular inflammation, lumen stenosis and plaque stability. The results showed that the levels of total cholesterol, triglycerol and low-density lipoprotein-cholesterol in plasma were not changed in all mice fed with high-fat diet, but the level of high-density lipoprotein-cholesterol was lower and the atherosclerosis index was significantly increased in HD + anti-β 2 GPI group than in other high-fat diet groups. In addition, compared with NR IgG-treated mice, anti-β 2 GPI IgG-treated mice showed more lipid deposition in the carotid artery, markedly narrowed arteriolar lumen as well as higher MMP-9 expression, more macrophages and fewer collagen fibers in the aortic arch root. Furthermore, the aortic mRNA levels of TNF-α, IL-1β, and MCP-1 were significantly increased in anti-β 2 GPI IgG-treated mice. Together, these data indicate that anti-β 2 GPI IgG increases vascular inflammation, aggravates atherosclerosis and promotes the formation of vulnerable plaque in ApoE-deficient mice.