Association of decreased serum sTREM-1 level with the severity of coronary artery disease: Inhibitory effect of sTREM-1 on TNF-α- and oxLDL-induced inflammatory reactions in endothelial cells

Soluble triggering receptor expressed on myeloid cells 1 (sTREM-1) is closely involved in autoimmune diseases and inflammatory reactions. We aimed to investigate whether serum sTREM-1 is related to coronary artery disease (CAD) and to evaluate the biological effects of sTREM-1 in cell experiments. This cross-sectional study included 263 consecutive patients with angiographically documented CAD, who were admitted for diagnosis and interventional treatment of CAD (CAD group), with 162 participants without CAD serving as controls (control group). Serum levels of sTREM-1 and high sensitivity C reactive protein (hsCRP) were determined in all participants. In cell experiments, the influence of sTREM-1 on tumor necrosis factor-α (TNF-α)- or oxidized low-density lipoprotein (oxLDL)-induced inflammatory reactions was evaluated in human umbilical vein endothelial cells (HUVECs). Serum level of sTREM-1 was significantly lower in CAD patients than in controls (P < 0.001). sTREM-1 values were related to the number of diseased coronary arteries (Spearman r = −0.413, P < 0.001) and the severity represented by Gensini score (Pearson r = −0.336, P < 0.001). Multivariable logistic regression analysis revealed that decreased sTREM-1 were independent determinants of CAD (OR = 0.428, P < 0.001). In cell experiments, recombinant sTREM-1 protein concentration-dependently inhibited the expression of IL-1β, IL-6, TNF-α, VCAM-1, and ICAM-1 induced by TNF-α or oxLDL in HUVECs. This study demonstrates that decreased serum sTREM-1 level is significantly associated with the presence and severity of CAD. sTREM-1 restrains inflammatory reaction in endothelial cells, suggesting that it might be a potential vascular protective factor.