Serotonin receptor type 2B activation augments TNF-α-induced matrix mineralization in murine valvular interstitial cells.
Serotonin receptor type 2B activation augments TNF-α-induced matrix mineralization in murine valvular interstitial cells.
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5-羟色胺受体2B激活增强TNF-α诱导的小鼠瓣膜间质细胞基质矿化
DOI：
10.1002/jcb.29847
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发表时间：
2021-03
影响因子：
4
通讯作者：
Tintut Y
中科院分区：
文献类型：
--
作者：
Fong F;Xian J;Demer LL;Tintut Y
钙化、纤维化和慢性炎症是钙化性主动脉瓣疾病的主要特征，这是一种危及生命的疾病。已知诱导5-羟色胺（5-HT）的药物会损害瓣膜，而携带外周5-羟色胺的活化血小板会促进钙化性主动脉瓣狭窄。然而，5-HT在瓣叶病理学中的作用尚不清楚。我们测试了血清素是否介导瓣膜细胞中炎症诱导的基质矿化。实时荧光定量RT-PCR分析表明，小鼠主动脉瓣间质细胞（VIC）表达两种5-羟色胺受体类型2A和2B（Htr 2a和Htr 2b）。尽管基线时Htr 2a表达更高，但促钙化TNF-α治疗诱导的Htr 2b表达是Htr 2a的数倍。5-HT也能促进TNF-α诱导的维克成骨细胞分化和基质矿化，但单独使用5-HT无此作用。在维克中使用特异性抑制剂或慢病毒敲低抑制2B型5-羟色胺受体，减弱了5-HT对TNF-α诱导的成骨细胞分化和矿化的影响。5-HT处理也增加了TNF-α诱导的基质金属蛋白酶-3的表达，这也被Htr 2b敲低所减弱。高脂血症Apoe−/−小鼠的主动脉根部Htr 2b表达和外周5-HT的血清水平也高于对照组正常脂血症小鼠。这些发现提示5-羟色胺信号在炎症诱导的钙化性瓣膜病中的新作用。
Calcification, fibrosis and chronic inflammation are the predominant features of calcific aortic valve disease, a life-threatening condition. Drugs that induce serotonin (5-HT) are known to damage valves, and activated platelets, which carry peripheral serotonin, are known to promote calcific aortic valve stenosis. However, the role of 5-HT in valve leaflet pathology is not known. We tested whether serotonin mediates inflammation-induced matrix mineralization in valve cells. Realtime RT-PCR analysis showed that murine aortic valve interstitial cells (VICs) expressed both serotonin receptor types 2A and 2B (Htr2a and Htr2b). Although Htr2a expression was greater at baseline, Htr2b expression was induced several-fold more than Htr2a in response to the pro-calcific TNF-α treatment. 5-HT also augmented TNF-α-induced osteoblastic differentiation and matrix mineralization of VIC, but 5-HT alone had no effects. Inhibition of serotonin receptor type 2B, using specific inhibitors or lentiviral knockdown in VIC, attenuated 5-HT effects on TNF-α-induced osteoblastic differentiation and mineralization. 5-HT treatment also augmented TNF-α-induced matrix metalloproteinase-3 expression, which was also attenuated by Htr2b knockdown. Htr2b expression in aortic roots and serum levels of peripheral 5-HT were also greater in the hyperlipidemic Apoe−/− mice than in control normolipemic mice. These findings suggest a new role for serotonin signaling in inflammation–induced calcific valvulopathy.
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影响因子：
15.9
作者：
GALIS, ZS;SUKHOVA, GK;LIBBY, P
通讯作者：
LIBBY, P
DOI：
10.2967/jnumed.114.152355
发表时间：
2015-06
期刊：
Journal of nuclear medicine : official publication, Society of Nuclear Medicine
影响因子：
--
作者：
Jung JJ;Razavian M;Challa AA;Nie L;Golestani R;Zhang J;Ye Y;Russell KS;Robinson SP;Heistad DD;Sadeghi MM
通讯作者：
Sadeghi MM
影响因子：
2.1
作者：
Freise C;Kretzschmar N;Querfeld U
通讯作者：
Querfeld U
DOI：
10.1016/j.bbrc.2004.05.181
发表时间：
2004-07-23
影响因子：
3.1
作者：
Cola, C;Almeida, M;Mehta, JL
通讯作者：
Mehta, JL
影响因子：
4.8
作者：
Lai, Chung-Fang;Shao, Jian-Su;Towler, Dwight A.
通讯作者：
Towler, Dwight A.