Establishment of an interleukin-1β-induced inflammation-activated endothelial cell-smooth muscle cell-mononuclear cell co-culture model and evaluation of the anti-inflammatory effects of tanshinone IIA on atherosclerosis.
Increasing evidence supports the hypothesis that inflammatory reactions serves an important function in the formation, progression and plaque rupture of atherosclerosis. Interleukin (IL)-1 primarily induces inflammation and is closely associated with the inflammatory environment and the formation of atherosclerosis. The present study aimed to establish an in vitro model for the evaluation of drug efficacy in the intervention of atherosclerosis from the inflammatory perspective, and to observe the anti-inflammatory effects of tanshinone IIA and andrographolide on atherosclerosis. The IL-1β-induced inflammation-activated endothelial cell (EC)-smooth muscle cell (SMC)-mononuclear cell (MC) co-culture model was established, based on the changes in a series of atherosclerosis-associated inflammatory markers secreted by ECs and SMCs. The expression of connexin in ECs, adhesion of MCs and changes in inflammatory signalling molecules were selected as evaluation indices for the inﬂammatory microenvironment of atherosclerosis. The use of this model revealed that tanshinone IIA exhibited significant efficacy against atherosclerosis and its inflammatory reactions. Inflammatory reactions were regarded as the primary mechanism underlying atherosclerosis. The established model simulated a series of relevant changes in the arterial wall under the inflammatory cytokines with oxidized low-density lipoprotein during the atherosclerotic process. The present study presented a reliable method for the identification of drugs with potential anti-inflammatory activity in atherosclerosis, for investigating the mechanisms of action, considering the improvement of the inflammatory state and the increase in plaque stability observed.
Department of Pharmacokinetics of Chinese Materia Medica, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, P.R. China.
Yujie
Y
Li
Department of Pharmacokinetics of Chinese Materia Medica, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, P.R. China.
Yan
Y
Guo
Department of Pharmacokinetics of Chinese Materia Medica, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, P.R. China.
Ying
Y
Chen
Department of Pharmacokinetics of Chinese Materia Medica, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, P.R. China.
Yajie
Y
Wang
Department of Pharmacokinetics of Chinese Materia Medica, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, P.R. China.
Yun
Y
You
Department of Pharmacokinetics of Chinese Materia Medica, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, P.R. China.
Qing
Q
Yang
Department of Pharmacokinetics of Chinese Materia Medica, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, P.R. China.
Xiaogang
X
Weng
Department of Pharmacokinetics of Chinese Materia Medica, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, P.R. China.
Qi
Q
Li
Department of Pharmacokinetics of Chinese Materia Medica, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, P.R. China.
Xiaoxin
X
Zhu
Department of Pharmacokinetics of Chinese Materia Medica, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, P.R. China.
Bingbing
B
Zhou
Department of Pharmacokinetics of Chinese Materia Medica, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, P.R. China.
Xucen
X
Liu
Department of Pharmacokinetics of Chinese Materia Medica, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, P.R. China.
Zaipeng
Z
Gong
Department of Pharmacokinetics of Chinese Materia Medica, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, P.R. China.
Ruijie
R
Zhang
D045784:Abietanes / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology; D000069059:Atorvastatin / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D017630:Connexins / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004224:Diterpenes / Q000494:pharmacology; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D053583:Interleukin-1beta / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000633:toxicity; D008954:Models, Biological; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism
D045784:Abietanes; D000893:Anti-Inflammatory Agents; D017630:Connexins; D016207:Cytokines; D004224:Diterpenes; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D008077:Lipoproteins, LDL; D016328:NF-kappa B; D047495:PPAR gamma; C099252:oxidized low density lipoprotein; C021751:tanshinone; D009569:Nitric Oxide; C030419:andrographolide; D000069059:Atorvastatin