HomeoboxC6 affects the apoptosis of human vascular endothelial cells and is involved in atherosclerosis

Apoptosis of vascular endothelial cells (VECs) is highly important in the occurrence and development of atherosclerosis (AS). HomeboxC6 (HOXC6) is expressed in higher levels in multiple malignant tissues, and it influences the malignant biological behavior of the cancer cells. However, the effects of HOXC6 on AS and the apoptosis of VECs have not been fully elucidated. In this study, we demonstrated that HOXC6 expression was increased in aortic wall of AS rats and peripheral blood monocytes of patients with coronary heart disease. Furthermore, it was uncovered that BAX expression was upregulated, while BCL-2 expression was downregulated in the aortic wall of AS rats. The apoptosis of human VECs (HVECs) cultured normally or treated with oxidized low-density lipoprotein in vitro was decreased after transfection withHOXC6-siRNA. Moreover, the results of Western blot analysis unveiled that the expressions of proapoptotic proteins, such as BAX, caspase-3, cleaved-caspase-3, and caspase-9 were reduced, while the expression of antiapoptotic protein, BCL-2, was elevated. Meanwhile, mRNA and protein expressions of phospholipase C beta (PLC beta) were decreased, the phosphorylation levels of protein kinase C zeta (PKC zeta) and nuclear transcription factor-kappa B-p65 (NF-kappa Bp65) and the membrane translocation of PKC zeta were reduced as well. Besides, the expression of interleukin-18 (IL-18) protein was downregulated. However, after overexpression of HOXC6, the opposite trends of the abovementioned indices were observed. Furthermore, the inhibition of apoptosis induced byHOXC6-siRNA was reversed by lysophosphatidylcholine, an activator of PKC zeta. Taken together, our results indicated that HOXC6 can promote the apoptosis of HVECs and may be involved in the occurrence and development of AS, which may be partially associated with the activation of PLC beta/PKC zeta/NF-kappa Bp65/IL-18 signaling pathway.

Automated summary

The study demonstrated that increased HOXC6 expression promotes apoptosis of HVECs, potentially contributing to the occurrence and development of atherosclerosis, partially through the activation of the PLC beta/PKC zeta/NF-kappa Bp65/IL-18 signaling pathway.