CROCETIN PROMOTES ANGIOGENESIS IN HUMAN ENDOTHELIAL CELLS THROUGH PI3K-AKT-ENOS SIGNALING PATHWAY

Nasirzadeh, M and Rasmi, Y and Rahbarghazi, R and Saboory, E and Shirpoor, A.R and Rezabakhsh, A and Zolali, E and Khalaji, N and Astinfeshan, M and Gholinejad, Z and Daeihasani, B and Kheradmand, F and Aramwit, P and Karimipour, M (2019) CROCETIN PROMOTES ANGIOGENESIS IN HUMAN ENDOTHELIAL CELLS THROUGH PI3K-AKT-ENOS SIGNALING PATHWAY. EXCLI Journal, 18. pp. 936-949.

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Abstract

Previous studies proved the pro-angiogenic effect of Crocetin, a natural carotenoid dicarboxylic acid, in both in vivo and in vitro models. However, the exact mechanism of Crocetin action has not completely been elucidated yet. The current experiment was designed to find the activity of PI3K-Akt-eNOS axis after the treatment of endo- thelial cells with Crocetin in vitro. Human Umbilical Vein Endothelial Cells (HUVECs) were incubated with various concentrations of Crocetin (1, 5, 25, 50, and 100 µM) over a period of 72 h. Crocetin significantly increased HUVECs viability after 72 h as compared with the control group. We also found that Crocetin promoted the formation of the capillary-like structure compared to the control (p<0.05). Moreover, an improved migration rate and increased MMP-9 activity were observed in HUVECs that received 50 µM Crocetin (p<0.05). Crocetin en- hanced the uptake of Ac-LDL which is correlated with increased lipid metabolism. Based on the data from the current experiment, protein level of VEGFR-1, -2 and p-Akt/Akt, p-eNOS/eNOS ratios were increased 72 h after the treatment of HUVECs with Crocetin (p<0.05). In contrast, the transcription level of VEGF was reduced in

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