Limits...
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.


Lovastatin protects HUVECs against ox-LDL-induced cytotoxicity. Cells were treated with 20 µg/ml ox-LDL, 0.5 µM lovastatin or a combination of both for 24 h. (A) Cell viability was determined using the cell counting kit-8 assay. (B) Cell apoptosis was assessed by Annexin V and PI staining, followed by flow cytometry. (C) Percentage of apoptotic cells. (D) Protein expression was analyzed by western blotting and band intensities were determined using ImageJ software, following normalization to a control (β-actin). Data are presented as the mean ± standard deviation of three independent experiments. *P<0.05 vs. the control cells; #P<0.05 vs. the ox-LDL group. HUVECs, human umbilical vein endothelial cells; ox-LDL, oxidized low-density lipoprotein; PI, propidium iodide.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4998215&req=5

f3-etm-0-0-3547: Lovastatin protects HUVECs against ox-LDL-induced cytotoxicity. Cells were treated with 20 µg/ml ox-LDL, 0.5 µM lovastatin or a combination of both for 24 h. (A) Cell viability was determined using the cell counting kit-8 assay. (B) Cell apoptosis was assessed by Annexin V and PI staining, followed by flow cytometry. (C) Percentage of apoptotic cells. (D) Protein expression was analyzed by western blotting and band intensities were determined using ImageJ software, following normalization to a control (β-actin). Data are presented as the mean ± standard deviation of three independent experiments. *P<0.05 vs. the control cells; #P<0.05 vs. the ox-LDL group. HUVECs, human umbilical vein endothelial cells; ox-LDL, oxidized low-density lipoprotein; PI, propidium iodide.

Mentions: Since lovastatin did not affect the viability of HUVECs after 24 h of treatment, the ability of lovastatin to protect HUVECs against ox-LDL-induced cytotoxicity was investigated. As is shown in Fig. 3A, 20 µg/ml ox-LDL significantly reduced the viability of HUVECs after 24 h of treatment (P<0.05). Although lovastatin did not significantly affect the viability of HUVECs after 24 h of treatment, it was able to significantly protect HUVECs against ox-LDL-induced injury (P<0.05). In addition, the ability of lovastatin to protect HUVECs against ox-LDL-induced apoptosis was evaluated (Fig. 3B and C). Annexin V-positive cells were significantly decreased in the lovastatin plus ox-LDL group, as compared with the ox-LDL group (P<0.05; Fig. 3C), thus further supporting the protective role of lovastatin against ox-LDL-induced HUVEC cytotoxicity.


Lovastatin exerts protective effects on endothelial cells via upregulation of PTK2B
Lovastatin protects HUVECs against ox-LDL-induced cytotoxicity. Cells were treated with 20 µg/ml ox-LDL, 0.5 µM lovastatin or a combination of both for 24 h. (A) Cell viability was determined using the cell counting kit-8 assay. (B) Cell apoptosis was assessed by Annexin V and PI staining, followed by flow cytometry. (C) Percentage of apoptotic cells. (D) Protein expression was analyzed by western blotting and band intensities were determined using ImageJ software, following normalization to a control (β-actin). Data are presented as the mean ± standard deviation of three independent experiments. *P<0.05 vs. the control cells; #P<0.05 vs. the ox-LDL group. HUVECs, human umbilical vein endothelial cells; ox-LDL, oxidized low-density lipoprotein; PI, propidium iodide.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4998215&req=5

f3-etm-0-0-3547: Lovastatin protects HUVECs against ox-LDL-induced cytotoxicity. Cells were treated with 20 µg/ml ox-LDL, 0.5 µM lovastatin or a combination of both for 24 h. (A) Cell viability was determined using the cell counting kit-8 assay. (B) Cell apoptosis was assessed by Annexin V and PI staining, followed by flow cytometry. (C) Percentage of apoptotic cells. (D) Protein expression was analyzed by western blotting and band intensities were determined using ImageJ software, following normalization to a control (β-actin). Data are presented as the mean ± standard deviation of three independent experiments. *P<0.05 vs. the control cells; #P<0.05 vs. the ox-LDL group. HUVECs, human umbilical vein endothelial cells; ox-LDL, oxidized low-density lipoprotein; PI, propidium iodide.
Mentions: Since lovastatin did not affect the viability of HUVECs after 24 h of treatment, the ability of lovastatin to protect HUVECs against ox-LDL-induced cytotoxicity was investigated. As is shown in Fig. 3A, 20 µg/ml ox-LDL significantly reduced the viability of HUVECs after 24 h of treatment (P<0.05). Although lovastatin did not significantly affect the viability of HUVECs after 24 h of treatment, it was able to significantly protect HUVECs against ox-LDL-induced injury (P<0.05). In addition, the ability of lovastatin to protect HUVECs against ox-LDL-induced apoptosis was evaluated (Fig. 3B and C). Annexin V-positive cells were significantly decreased in the lovastatin plus ox-LDL group, as compared with the ox-LDL group (P<0.05; Fig. 3C), thus further supporting the protective role of lovastatin against ox-LDL-induced HUVEC cytotoxicity.

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.