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. 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.
Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, No. 1 Yixueyuan Road, Yuzhong District, Chongqing 400016, China.
Peng
0000-0002-9702-2550
P
Zhang
Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, No. 1 Yixueyuan Road, Yuzhong District, Chongqing 400016, China.
Xin
0000-0003-1349-0275
X
Xing
Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, No. 1 Yixueyuan Road, Yuzhong District, Chongqing 400016, China.
Chunxiao
0000-0001-5841-3789
C
Hu
Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, No. 1 Yixueyuan Road, Yuzhong District, Chongqing 400016, China.
Hui
0000-0002-6644-550X
H
Yu
Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, No. 1 Yixueyuan Road, Yuzhong District, Chongqing 400016, China.
Qian
0000-0001-7846-7741
Q
Dong
Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, No. 1 Yixueyuan Road, Yuzhong District, Chongqing 400016, China.
Guanglei
G
Chang
Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, No. 1 Yixueyuan Road, Yuzhong District, Chongqing 400016, China.
Shu
0000-0002-9986-1630
S
Qin
Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, No. 1 Yixueyuan Road, Yuzhong District, Chongqing 400016, China.
Jian
0000-0002-8889-172X
J
Liu
Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, No. 1 Yixueyuan Road, Yuzhong District, Chongqing 400016, China.
Dongying
0000-0003-0453-1004
D
Zhang
D000818:Animals; D001093:Arachidonate 15-Lipoxygenase / Q000235:genetics / Q000378:metabolism*; D000069059:Atorvastatin / Q000494:pharmacology*; D002339:Carotid Arteries / Q000187:drug effects* / Q000378:metabolism*; D002340:Carotid Artery Diseases / Q000188:drug therapy / Q000378:metabolism; D049109:Cell Proliferation / Q000235:genetics / Q000502:physiology; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000069059:Atorvastatin; D001093:Arachidonate 15-Lipoxygenase