Citreoviridin Enhances Atherogenesis in Hypercholesterolemic ApoE-Deficient Mice via Upregulating Inflammation and Endothelial Dysfunction.
Vascular endothelial dysfunction and inflammatory response are early events during initiation and progression of atherosclerosis. In vitro studies have described that CIT markedly upregulates expressions of ICAM-1 and VCAM-1 of endothelial cells, which result from NF-κB activation induced by CIT. In order to determine whether it plays a role in atherogenesis in vivo, we conducted the study to investigate the effects of CIT on atherosclerotic plaque development and inflammatory response in apolipoprotein E deficient (apoE-/-) mice. Five-week-old apoE-/- mice were fed high-fat diets and treated with CIT for 15 weeks, followed by assay of atherosclerotic lesions. Nitric oxide (NO), vascular endothelial growth factor (VEGF) and endothelin-1 (ET-1) were detected in serum. Levels of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), VEGF, and ET-1 in plaque areas of artery walls were examined. NF-κB p65 expression and NF-κB activation in aorta also were assessed. CIT treatment significantly augmented atherosclerotic plaques and increased expressions of ICAM-1, VCAM-1, VEGF and ET-1 in aorta. Mechanistic studies showed that activation of NF-κB was significantly elevated by CIT treatment, indicating the effect of CIT on atherosclerosis may be regulated by activation of NF-κB.
School of Public Health, Taishan Medical University, Taian 271000, China; School of Public Health, Shandong University, Jinan 250012, China.
Hai-Feng
HF
Hou
School of Public Health, Taishan Medical University, Taian 271000, China.
Na
N
Yuan
Taian City Central Hospital, Taian 271000, China.
Qing
Q
Guo
School of Public Health, Taishan Medical University, Taian 271000, China.
Tao
T
Sun
Ruijin Hospital, College of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China.
Cheng
C
Li
School of Public Health, Taishan Medical University, Taian 271000, China.
Jian-Bao
JB
Liu
School of Public Health, Taishan Medical University, Taian 271000, China.
Qun-Wei
QW
Li
School of Public Health, Shandong University, Jinan 250012, China.
Bao-Fa
BF
Jiang
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency; D050197:Atherosclerosis / Q000097:blood / Q000150:complications*; D001313:Aurovertins / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D059305:Diet, High-Fat; D019332:Endothelin-1 / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D006937:Hypercholesterolemia / Q000097:blood / Q000150:complications*; D007249:Inflammation / Q000150:complications*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008297:Male; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D001057:Apolipoproteins E; D001313:Aurovertins; D019332:Endothelin-1; D008055:Lipids; D016328:NF-kappa B; D019010:Vascular Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; D018799:Intercellular Adhesion Molecule-1; D009569:Nitric Oxide; C014416:citreoviridin