15-Lipoxygenase-1 Is Involved in the Effects of Atorvastatin on Endothelial Dysfunction
Statins exert pleiotropic effects on endothelial cells in addition to lowering cholesterol. 15-Lipoxygenase-1 (ALOX15) has been implicated in vascular inflammation and disease. The relationship between atorvastatin and ALOX15 was investigated using a rat carotid artery balloon-injury model. Hematoxy...
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| Format: | Article |
| Language: | English |
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Wiley
2016-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2016/6769032 |
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| author | Peng Zhang Xin Xing Chunxiao Hu Hui Yu Qian Dong Guanglei Chang Shu Qin Jian Liu Dongying Zhang |
| author_facet | Peng Zhang Xin Xing Chunxiao Hu Hui Yu Qian Dong Guanglei Chang Shu Qin Jian Liu Dongying Zhang |
| author_sort | Peng Zhang |
| collection | DOAJ |
| description | Statins exert pleiotropic effects on endothelial cells in addition to lowering cholesterol. 15-Lipoxygenase-1 (ALOX15) has been implicated in vascular inflammation and disease. The relationship between atorvastatin and ALOX15 was investigated using a rat carotid artery balloon-injury model. Hematoxylin and eosin (HE) staining showed that ALOX15 overexpression increased the thickness of the intima-media (IMT). Immunohistochemistry and western blotting showed that atorvastatin increased the expression of cellular adhesion molecules (CAMs) but decreased the expression of endothelial nitric oxide synthase (eNOS); these effects of atorvastatin were blocked by ALOX15 overexpression. In human umbilical venous endothelial cells (HUVECs), silencing of ALOX15 enhanced the effects of atorvastatin on endothelial function. Expression levels of CAMs and Akt/eNOS/NO under oxidized low-density lipoprotein (ox-LDL) stimulation were modulated by ALOX15 inhibitor and ALOX15 small interfering RNA (siRNA). Atorvastatin abolished the activation of nuclear factor-kappa B (NF-κB) induced by ox-LDL. Exposure to ox-LDL induced upregulation of ALOX15 in HUVECs, but this effect was partially abolished by atorvastatin or the NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC). These results demonstrate that regulation of ALOX15 expression might be involved in the effects of atorvastatin on endothelial dysfunction. |
| format | Article |
| id | doaj-art-5eebd9936d1046e5b14650513cd7d017 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-5eebd9936d1046e5b14650513cd7d0172025-02-03T01:26:35ZengWileyMediators of Inflammation0962-93511466-18612016-01-01201610.1155/2016/6769032676903215-Lipoxygenase-1 Is Involved in the Effects of Atorvastatin on Endothelial DysfunctionPeng Zhang0Xin Xing1Chunxiao Hu2Hui Yu3Qian Dong4Guanglei Chang5Shu Qin6Jian Liu7Dongying Zhang8Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, No. 1 Yixueyuan Road, Yuzhong District, Chongqing 400016, ChinaDepartment of Cardiology, The First Affiliated Hospital of Chongqing Medical University, No. 1 Yixueyuan Road, Yuzhong District, Chongqing 400016, ChinaDepartment of Cardiology, The First Affiliated Hospital of Chongqing Medical University, No. 1 Yixueyuan Road, Yuzhong District, Chongqing 400016, ChinaDepartment of Cardiology, The First Affiliated Hospital of Chongqing Medical University, No. 1 Yixueyuan Road, Yuzhong District, Chongqing 400016, ChinaDepartment of Cardiology, The First Affiliated Hospital of Chongqing Medical University, No. 1 Yixueyuan Road, Yuzhong District, Chongqing 400016, ChinaDepartment of Cardiology, The First Affiliated Hospital of Chongqing Medical University, No. 1 Yixueyuan Road, Yuzhong District, Chongqing 400016, ChinaDepartment of Cardiology, The First Affiliated Hospital of Chongqing Medical University, No. 1 Yixueyuan Road, Yuzhong District, Chongqing 400016, ChinaDepartment of Cardiology, The First Affiliated Hospital of Chongqing Medical University, No. 1 Yixueyuan Road, Yuzhong District, Chongqing 400016, ChinaDepartment of Cardiology, The First Affiliated Hospital of Chongqing Medical University, No. 1 Yixueyuan Road, Yuzhong District, Chongqing 400016, ChinaStatins exert pleiotropic effects on endothelial cells in addition to lowering cholesterol. 15-Lipoxygenase-1 (ALOX15) has been implicated in vascular inflammation and disease. The relationship between atorvastatin and ALOX15 was investigated using a rat carotid artery balloon-injury model. Hematoxylin and eosin (HE) staining showed that ALOX15 overexpression increased the thickness of the intima-media (IMT). Immunohistochemistry and western blotting showed that atorvastatin increased the expression of cellular adhesion molecules (CAMs) but decreased the expression of endothelial nitric oxide synthase (eNOS); these effects of atorvastatin were blocked by ALOX15 overexpression. In human umbilical venous endothelial cells (HUVECs), silencing of ALOX15 enhanced the effects of atorvastatin on endothelial function. Expression levels of CAMs and Akt/eNOS/NO under oxidized low-density lipoprotein (ox-LDL) stimulation were modulated by ALOX15 inhibitor and ALOX15 small interfering RNA (siRNA). Atorvastatin abolished the activation of nuclear factor-kappa B (NF-κB) induced by ox-LDL. Exposure to ox-LDL induced upregulation of ALOX15 in HUVECs, but this effect was partially abolished by atorvastatin or the NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC). These results demonstrate that regulation of ALOX15 expression might be involved in the effects of atorvastatin on endothelial dysfunction.http://dx.doi.org/10.1155/2016/6769032 |
| spellingShingle | Peng Zhang Xin Xing Chunxiao Hu Hui Yu Qian Dong Guanglei Chang Shu Qin Jian Liu Dongying Zhang 15-Lipoxygenase-1 Is Involved in the Effects of Atorvastatin on Endothelial Dysfunction Mediators of Inflammation |
| title | 15-Lipoxygenase-1 Is Involved in the Effects of Atorvastatin on Endothelial Dysfunction |
| title_full | 15-Lipoxygenase-1 Is Involved in the Effects of Atorvastatin on Endothelial Dysfunction |
| title_fullStr | 15-Lipoxygenase-1 Is Involved in the Effects of Atorvastatin on Endothelial Dysfunction |
| title_full_unstemmed | 15-Lipoxygenase-1 Is Involved in the Effects of Atorvastatin on Endothelial Dysfunction |
| title_short | 15-Lipoxygenase-1 Is Involved in the Effects of Atorvastatin on Endothelial Dysfunction |
| title_sort | 15 lipoxygenase 1 is involved in the effects of atorvastatin on endothelial dysfunction |
| url | http://dx.doi.org/10.1155/2016/6769032 |
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