Roles of prostanoids in the pathogenesis of cardiovascular diseases: Novel insights from knockout mouse studies.
Roles of prostanoids in the pathogenesis of cardiovascular diseases: Novel insights from knockout mouse studies.
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DOI：
10.1016/j.pharmthera.2010.09.004
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发表时间：
2011-02
影响因子：
13.5
通讯作者：
Koh-ichi Yuhki;Fumiaki Kojima;H. Kashiwagi;J. Kawabe;T. Fujino;S. Narumiya;F. Ushikubi
中科院分区：
文献类型：
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作者：
Koh-ichi Yuhki;Fumiaki Kojima;H. Kashiwagi;J. Kawabe;T. Fujino;S. Narumiya;F. Ushikubi
由前列腺素(PGs)和血栓素(TXs)组成的前列腺素类化合物是由细胞膜中的代表性脂肪酸花生四烯酸通过磷脂酶A2、环氧合酶和各自的前列腺素合成酶的顺序作用而产生的。前列腺素在生物合成后立即释放到细胞外，并在体内发挥广泛的作用。这些作用是由靶细胞中表达的G蛋白偶联受体介导的，这些受体分别包括前列腺素D_2、前列腺素E_2、前列腺素F_2α、前列环素和血栓素A_2的DP、EP、FP、IP和TP受体。此外，EP受体还有四种亚型：EP1、EP2、EP3和EP4。最近，前列腺素在心血管疾病发病机制中的作用已被广泛研究，利用缺乏每个前列腺素受体或参与前列腺素生物合成的酶的小鼠。这些研究揭示了前列腺素在心血管疾病发展中的重要和新的作用，如急性心肌梗死、心肌肥厚、动脉粥样硬化、血管重构、高血压和脑血栓形成。前列腺素在炎症性心动过速的发生和调节血小板功能中的作用也已被阐明。在这篇综述中，我们总结了从基因敲除小鼠研究中揭示的前列腺素的这些作用。
Prostanoids consisting of prostaglandins (PGs) and thromboxanes (TXs) are produced from arachidonic acids, representative fatty acids contained in cell membrane, by the sequential actions of phospholipase A2, cyclooxygenases and respective prostanoid synthases. Prostanoids are released outside of the cells immediately after biosynthesis and exert a wide range of actions in the body. These actions are mediated by their respective G protein-coupled receptors expressed in the target cells, which receptors include the DP, EP, FP, IP and TP receptors for PGD2, PGE2, PGF2α, PGI2and TXA2, respectively. In addition, there are four subtypes of the EP receptors: EP1, EP2, EP3and EP4. Recently, roles of prostanoids in the pathogenesis of cardiovascular diseases have been widely examined using mice lacking each prostanoid receptor individually or enzyme participating in prostanoid biosynthesis. These studies have revealed important and novel roles of prostanoids in the development of cardiovascular diseases, such as acute myocardial infarction, cardiac hypertrophy, atherosclerosis, vascular remodeling, hypertension and cerebral thrombosis. Roles of prostanoids in the generation of inflammatory tachycardia and the regulation of platelet function have also been clarified. In this review, we summarize these roles of prostanoids revealed from knockout mouse studies.