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Lovastatin exerts protective effects on endothelial cells via upregulation of PTK2B

View Article: PubMed Central - PubMed

ABSTRACT

Statins are HMG-CoA reductase inhibitors that are used to decrease the blood levels of low-density lipoprotein (LDL). In addition, they have been shown to exert pleiotropic protective effects in the absence of LDL-lowering activity. The present study investigated the effects of lovastatin on global gene expression in human umbilical vein endothelial cells (HUVECs), in order to further explore its ability to protect against oxidized (ox)-LDL-induced cytotoxicity. HUVECs were treated with lovastatin for 2–24 h, and gene expression patterns were analyzed using cDNA microarrays. The results suggested that numerous genes were regulated by lovastatin, including certain genes associated with cell survival, such as PTK2B, BCL2 and MAP3K3. In particular, PTK2B, which has been shown to exert anti-apoptotic effects against ox-LDL-induced cell injury, was upregulated by lovastatin. Knockdown of PTK2B was able to attenuate ox-LDL-induced cell injury, and this was associated with decreased levels of phosphorylated-AKT and eNOS, and inhibition of mitochondrial-dependent apoptosis. In conclusion, the results of the present study suggested that lovastatin protects against ox-LDL-induced cell injury, potentially via the upregulation of PTK2B, which regulates the anti-apoptosis signaling pathway.

No MeSH data available.


Effect of lovastatin on the cholesterol content and gene expression profile of HUVECs. (A) Lovastatin (0.1, 0.5, 2.5 and 12.5 µM) decreased the cholesterol content of HUVECs after 24 h of treatment. (B) 0.5 µM lovastatin decreased the cholesterol content of HUVECs following 12 and 24 h of treatment. (C) Genes that were differentially expressed at 2 and 24 h of lovastatin treatment (fold-change >1.5; false discovery rate <0.01; green indicates downregulation and red indicates upregulation). (D) Fold-change of regulated genes after 2 and 24 h of lovastatin treatment. Data are expressed as the mean ± standard deviation of three independent experiments. *P<0.05 vs. the control cells. HUVECs, human umbilical vein endothelial cells.
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f1-etm-0-0-3547: Effect of lovastatin on the cholesterol content and gene expression profile of HUVECs. (A) Lovastatin (0.1, 0.5, 2.5 and 12.5 µM) decreased the cholesterol content of HUVECs after 24 h of treatment. (B) 0.5 µM lovastatin decreased the cholesterol content of HUVECs following 12 and 24 h of treatment. (C) Genes that were differentially expressed at 2 and 24 h of lovastatin treatment (fold-change >1.5; false discovery rate <0.01; green indicates downregulation and red indicates upregulation). (D) Fold-change of regulated genes after 2 and 24 h of lovastatin treatment. Data are expressed as the mean ± standard deviation of three independent experiments. *P<0.05 vs. the control cells. HUVECs, human umbilical vein endothelial cells.

Mentions: The effect of lovastatin on intracellular cholesterol content was evaluated. Lovastatin (0.5, 2.5 and 12.5 µM) significantly decreased the cholesterol content of HUVECs following 24 h of incubation (P<0.05; Fig. 1A). Notably, the cholesterol content was not significantly different between the 0.5, 2.5 and 12.5 µM lovastatin-treated cells (P>0.05; Fig. 1A); therefore, 0.5 µM lovastatin was used for the time-course experiment. As shown in Fig. 1B, lovastatin significantly decreased the cholesterol content of HUVECs following 12 and 24 h of treatment (P<0.05), but not after 2 or 6 h of treatment (P>0.05). Therefore, the duration of treatment with 0.5 µM lovastatin was set at 2 and 24 h, in order to observe short- and long-term gene expression profiles, which may be dependent or independent of cholesterol lowering.


Lovastatin exerts protective effects on endothelial cells via upregulation of PTK2B
Effect of lovastatin on the cholesterol content and gene expression profile of HUVECs. (A) Lovastatin (0.1, 0.5, 2.5 and 12.5 µM) decreased the cholesterol content of HUVECs after 24 h of treatment. (B) 0.5 µM lovastatin decreased the cholesterol content of HUVECs following 12 and 24 h of treatment. (C) Genes that were differentially expressed at 2 and 24 h of lovastatin treatment (fold-change >1.5; false discovery rate <0.01; green indicates downregulation and red indicates upregulation). (D) Fold-change of regulated genes after 2 and 24 h of lovastatin treatment. Data are expressed as the mean ± standard deviation of three independent experiments. *P<0.05 vs. the control cells. HUVECs, human umbilical vein endothelial cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4998215&req=5

f1-etm-0-0-3547: Effect of lovastatin on the cholesterol content and gene expression profile of HUVECs. (A) Lovastatin (0.1, 0.5, 2.5 and 12.5 µM) decreased the cholesterol content of HUVECs after 24 h of treatment. (B) 0.5 µM lovastatin decreased the cholesterol content of HUVECs following 12 and 24 h of treatment. (C) Genes that were differentially expressed at 2 and 24 h of lovastatin treatment (fold-change >1.5; false discovery rate <0.01; green indicates downregulation and red indicates upregulation). (D) Fold-change of regulated genes after 2 and 24 h of lovastatin treatment. Data are expressed as the mean ± standard deviation of three independent experiments. *P<0.05 vs. the control cells. HUVECs, human umbilical vein endothelial cells.
Mentions: The effect of lovastatin on intracellular cholesterol content was evaluated. Lovastatin (0.5, 2.5 and 12.5 µM) significantly decreased the cholesterol content of HUVECs following 24 h of incubation (P<0.05; Fig. 1A). Notably, the cholesterol content was not significantly different between the 0.5, 2.5 and 12.5 µM lovastatin-treated cells (P>0.05; Fig. 1A); therefore, 0.5 µM lovastatin was used for the time-course experiment. As shown in Fig. 1B, lovastatin significantly decreased the cholesterol content of HUVECs following 12 and 24 h of treatment (P<0.05), but not after 2 or 6 h of treatment (P>0.05). Therefore, the duration of treatment with 0.5 µM lovastatin was set at 2 and 24 h, in order to observe short- and long-term gene expression profiles, which may be dependent or independent of cholesterol lowering.

View Article: PubMed Central - PubMed

ABSTRACT

Statins are HMG-CoA reductase inhibitors that are used to decrease the blood levels of low-density lipoprotein (LDL). In addition, they have been shown to exert pleiotropic protective effects in the absence of LDL-lowering activity. The present study investigated the effects of lovastatin on global gene expression in human umbilical vein endothelial cells (HUVECs), in order to further explore its ability to protect against oxidized (ox)-LDL-induced cytotoxicity. HUVECs were treated with lovastatin for 2&ndash;24 h, and gene expression patterns were analyzed using cDNA microarrays. The results suggested that numerous genes were regulated by lovastatin, including certain genes associated with cell survival, such as PTK2B, BCL2 and MAP3K3. In particular, PTK2B, which has been shown to exert anti-apoptotic effects against ox-LDL-induced cell injury, was upregulated by lovastatin. Knockdown of PTK2B was able to attenuate ox-LDL-induced cell injury, and this was associated with decreased levels of phosphorylated-AKT and eNOS, and inhibition of mitochondrial-dependent apoptosis. In conclusion, the results of the present study suggested that lovastatin protects against ox-LDL-induced cell injury, potentially via the upregulation of PTK2B, which regulates the anti-apoptosis signaling pathway.

No MeSH data available.