IL-17 induces apoptosis of vascular endothelial cells — A potential mechanism for human acute coronary syndrome

Th17 cells producing IL-17 are involved in the pathogenesis of atherosclerosis, but the underlying mechanisms remain unclear. In this study, we investigated the effects of IL-17 on human vascular endothelial cells and showed that IL-17 induced cell death of the vascular endothelial cells, which played a pivotal role in plaque destabilization triggering acute coronary syndrome (ACS). We showed that circulating Th17 cells and IL-17 increased in patients with ACS compared to the patients with stable angina or health individuals; the plasma levels of IL-6 increased but TGF-β decreased in ACS patients, exhibiting a positive and negative correlation with that of IL-17, respectively. Importantly, we uncovered that IL-17 promoted the production of von Willebrand factor by endothelial cells and induced endothelial apoptosis by activating caspase-3, caspase-9 and up-regulating the ratio of Bax/Bcl-2, indicating the function of IL-17 in vascular endothelial damage as a potential mechanism for the pathogenesis of human ACS.

► Increase in circulating Th17 cells and IL-17 in patients with ACS.
► Positive correlation of plasma IL-17 with IL-6 in ACS and SA patients.
► Negative correlation of plasma IL-17 with TGF-β in ACS and SA patients.
► IL-17 damages endothelium via inducing VWF secretion by endothelial cells.
► IL-17 induces apoptosis of endothelial cells through mitochondrial pathway.