Expression of thromboxane synthase, prostacyclin synthase and thromboxane receptor in atherosclerotic lesions: Correlation with plaque composition
Expression of thromboxane synthase, prostacyclin synthase and thromboxane receptor in atherosclerotic lesions: Correlation with plaque composition
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DOI：
10.1016/j.atherosclerosis.2009.08.008
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发表时间：
2010-02-01
期刊：
影响因子：
5.3
通讯作者：
Pratico, Domenico
中科院分区：
文献类型：
--
作者：
Cyrus, Tillmann;Ding, Tao;Pratico, Domenico
目的：前列腺素，如血栓素A(2) （TxA(2)）和前列环素（PGI(2)）是生物活性脂质介质，与动脉粥样硬化的发病机制有关。在本研究中，我们验证了血栓素合成酶（TXAS）、前列环素合成酶（PGIS）和血栓素受体（TP）在动脉粥样硬化病变内表达的假设。方法：从高脂饮食的低密度脂蛋白受体缺乏（LDL - ko）小鼠中获得动脉粥样硬化主动脉段。采用实时定量反转录PCR、免疫组化检测TXAS、PGIS、TP的表达水平；同时测定了TxA(2)和PGI(2)的生物合成。结果：脂肪饮食8周后，与对照组相比，LDL - ko小鼠主动脉弓的PGIS、TXAS、TP mRNA、TxA(2)和PGI(2)水平显著增加。相比之下，高脂饮食16周后，PGIS和PGI(2)显著降低，而与8周组相比，动脉粥样硬化组织中的TXAS和TP信息以及蛋白和TxA(2)水平进一步显著升高。这些变化与动脉粥样硬化病变的细胞组成有关。结论：TXAS、PGIS和TP均存在于动脉粥样硬化病变区域，它们的水平随着动脉粥样硬化的进展而改变，并参与TxA(2)和PGI(2)的形成。2009爱思唯尔爱尔兰有限公司版权所有。
Objectives: Prostaglandins, such as thromboxane A(2) (TxA(2)) and prostacyclin (PGI(2)), are bioactive lipid mediators that are implicated in the pathogenesis of atherosclerosis. In the current study, we tested the hypothesis that thromboxane synthase (TXAS), prostacyclin synthase (PGIS) and thromboxane receptor (TP) are expressed within the atherosclerotic lesion.Methods: Atherosclerotic aorta segments were obtained from low-density lipoprotein receptor deficient (LDL r-KO) mice on a high fat diet. Expression levels of TXAS, PGIS and TP were evaluated by real-time quantitative reverse transcription PCR, and immunohistochemistry; TxA(2) and PGI(2) biosynthesis was also assayed.Results: After 8 weeks on the fat diet, aortic arches from LDL r-KO mice showed a significant increase in PGIS, TXAS, TP mRNA, TxA(2) and PGI(2) levels, when compared with controls. By contrast, after 16 weeks on the high fat diet PGIS and PGI(2) were significantly reduced, whereas TXAS and TP message and protein and TxA(2) levels were further and significantly increased in the atherosclerotic tissues when compared with the 8-week group. These changes correlated with the cellular composition of the atherosclerotic lesions.Conclusions: TXAS, PGIS and TP are all present within the atherosclerotic lesion areas, their levels change during progression of atherogenesis and contribute to TxA(2) and PGI(2) formation. (C) 2009 Elsevier Ireland Ltd. All rights reserved.