Interleukin-1β mediates high glucose induced phenotypic transition in human aortic endothelial cells

Citations of this article
Mendeley users who have this article in their library.


BACKGROUND: Previous studies have shown that high glucose (HG) induced endothelial cell (EC) damage via a phenotypic transition of EC. There is increasing evidence suggesting the role of inflammatory cytokines in mediated HG-induced EC damage. However, little is known about the potential role of interleukin-1beta (IL-1beta) in the process. The aim of present study was to investigate whether IL-1beta mediated HG-induced phenotypic transition in human aortic endothelial cells (HAECs) and to determine the possible underlying mechanism. METHODS: Primary HAECs were exposed to normal glucose (NG, 5.5 nM), high glucose (HG,30 nM), IL-1beta (10 ng/ml), HG + IL-1beta (10 ng/ml) and HG + anti-IL-1beta antibodies (1000 ng/ml) or HG + IL-1beta small interfering RNA (siRNA). Pathological changes were investigated using confocal microscopy and electron microscopy. Confocal microscopy was performed to detect the co-expression of CD31 and fibroblast specific protein 1 (FSP1). To study the effect of protein kinase C-beta (PKCbeta) activation on IL-1beta in HAECs, HAECs were stimulated with 30 nM PMA (PKCbeta activator) and 0.3 muM PKCbeta inhibition (LY317615) for 48 h in the NG or HG group. The expressions of PKCbeta and IL-1beta were detected by RT-PCR and Western blot. And the concentration of IL-1beta in the supernatant of HAECs was measured by ELISA. The expressions of FSP1, a-SMA and CD31 were detected by Western blot. RESULTS: It was shown that the HG resulted in significant increase in the expressions of PKCbeta and IL-1beta in dose-and time-dependent manners. The HG or exogenous IL-1beta alone inhibited the expression of CD31 and markly increased the expressions of FSP1 and alpha-SMA. Furthermore, we observed that the HG and IL-1beta synergistically increased FSP1 and a-SMA expressions compared with the HG or IL-1beta alone group (P < 0.05). Confocal microscopy revealed a colocalization of CD31 and FSP1 and that some cells acquired spindle-shaped morphologies and a loss of CD31 staining. Electron microscopy showed that the HG resulted in the increased microfilamentation and a roughened endoplasmic reticulum structure in the cytoplasm. However, the changes above were attenuated by the intervention of anti-IL-1beta antibodies or IL-1beta siRNA (P < 0.05). In addition, the PMA induced the expressions of PKCbeta and IL-1beta in HAECs. The PKCbeta activation may mediate the effect of the HG on IL-1beta production, which could be attenuated by the PKCbeta selective inhibitor (LY317615) (P < 0.05). CONCLUSIONS: Our findings suggested that HG-induced phenotypic transition of HAECs might require IL-beta activation via the PKCbeta pathway.




Zhu, D. D., Tang, R. N., Lv, L. L., Wen, Y., Liu, H., Zhang, X. L., … Liu, B. C. (2016). Interleukin-1β mediates high glucose induced phenotypic transition in human aortic endothelial cells. Cardiovascular Diabetology, 15(1).

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free