Tanshinone IIA Prevents Rat Basilar Artery Smooth Muscle Cells Proliferation by Inactivation of PDK1 During the Development of Hypertension.
Basilar vascular smooth muscle cells (BASMCs) hyperplasia is a prominent feature of cerebrovascular remodeling and stroke during the development of hypertension. Tanshinone IIA (Tan) has been reported to exhibit a protective effect against the pathological features of hypertension. Previous studies have shown that phosphoinostitide-3 kinase (PI3K)/3'-phosphoinostitide dependent kinase (PDK1)/AKT pathway is involved in the regulation of proliferation of various cell types. Therefore, there may be a crosstalk between Tan antihypertension processes and PI3K/PDK1/AKT proliferative effect in BASMCs. To test this hypothesis, we used a 2-kidney, 2-clip hypertension model to examine the effect of Tan on PI3K/PDK1/AKT pathway by cellular, molecular, and biochemical approaches. Our results revealed that the abundance of PDK1 in plasma was paralleled with an increase in blood pressure and the cross-sectional area of basilar artery in hypertensive rats. Tan decreased blood pressure and hypertension-induced PDK1 phosphorylation but produced no effect on the phosphorylation of PI3K. Moreover, Tan attenuated endothelin 1 induced the activation of PDK1/AKT pathway in rat BASMCs. Tan could inhibit cell cycle transition by regulating the expression of cyclin D1 and p27, in turn, prevent proliferation of BASMCs. Our study provides a novel mechanism by which Tan prevents cerebrovascular cell proliferation during hypertension, and thus Tan may be a potential therapeutic agent for cerebrovascular remodeling and stroke.
Department of Neurology, Shanghai Seventh People's Hospital, Shanghai, China yuzlmed@163.com.
Zhi-Liang
ZL
Yu
Department of Rehabilitation Medicine, Shanghai Seventh People's Hospital, Shanghai, China.
Jie-Ning
JN
Wang
Department of Neurology, Shanghai Seventh People's Hospital, Shanghai, China.
Xiao-Hua
XH
Wu
Department of Neurology, Changhai Hospital, Second Military Medical University, Shanghai, China.
Hui-Jun
HJ
Xie
Department of Neurology, Shanghai Seventh People's Hospital, Shanghai, China.
Ying
Y
Han
Department of Neurology, Changhai Hospital, Second Military Medical University, Shanghai, China.
Yang-Tai
YT
Guan
Department of Neurology, Shanghai Seventh People's Hospital, Shanghai, China.
Yong
Y
Qin
Department of Neurology, Changhai Hospital, Second Military Medical University, Shanghai, China.
Jian-Ming
JM
Jiang
D000818:Animals; D001488:Basilar Artery / Q000166:cytology* / Q000473:pathology; D001572:Benzofurans / Q000494:pharmacology*; D001794:Blood Pressure; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D019938:Cyclin D1 / Q000096:biosynthesis / Q000235:genetics; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000096:biosynthesis / Q000235:genetics; D019332:Endothelin-1 / Q000097:blood; D006973:Hypertension / Q000473:pathology*; D006978:Hypertension, Renovascular / Q000473:pathology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000473:pathology; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D051381:Rats; D017207:Rats, Sprague-Dawley
D001572:Benzofurans; C530106:Ccnd1 protein, rat; C493962:Cdkn1b protein, rat; D019332:Endothelin-1; C000631434:Pdk1 protein, rat; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; C530742:tashinone IIA; D019938:Cyclin D1; D050760:Cyclin-Dependent Kinase Inhibitor p27; D017346:Protein Serine-Threonine Kinases
PDK1; basilar vascular smooth muscle cells; endothelin 1; hypertension; proliferation; tanshinone IIA