Secretory vimentin is associated with coronary artery disease in patients and induces atherogenesis in ApoE−/− mice

Purpose The present study aimed to investigate the relationship between serum levels of secretory vimentin and coronary artery disease (CAD). The biological effect of secretory vimentin was ascertained by experiments. Methods We analysed serum levels of secretory vimentin in CAD patients (n = 288) and non-CAD controls (n = 195) by ELISA. To evaluate the pro-inflammatory effects of secreted vimentin, the human aortic endothelial cells (HAECs) and human peripheral blood mononuclear cells (PBMCs) were treated with recombinant vimentin or saline. Intraperitoneal injection of vimentin (1 μg/each) or saline was performed every other day for 12 weeks in ApoE−/− mice for assessment of atherogenic effect. Results Serum levels of secretory vimentin were significantly increased in CAD patients than in health controls (p < 0.05), and correlated with the number of diseased coronary arteries, Syntax and Gensini score (for all comparison, p < 0.01). Logistic regression analysis showed that vimentin level is an independent determinant of CAD. In experiments, recombinant vimentin protein enhanced the expression of adhesion molecules and inflammatory cytokines in both endothelial cells and macrophages. This protein also promoted macrophage-endothelial cells adhesion in vitro and the recruitment of leukocytes to mesenteric venules in C57BL/6 mice. Compared with saline, intraperitoneal injection of recombinant vimentin (1 μg/each) every other day induced atherogenesis in ApoE−/− mice at 12-weeks, with significant increase of inflammatory cytokine and adhesion molecules expression in aortic tissue (p < 0.05). Conclusion Serum vimentin levels are associated with the presence and the severity of CAD. Vimentin protein promotes atherogenesis in ApoE−/− mice.