Roles of prostanoids in the pathogenesis of cardiovascular diseases.
Roles of prostanoids in the pathogenesis of cardiovascular diseases.
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发表时间：
2010-04
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通讯作者：
Koh-ichi Yuhki;H. Kashiwagi;Fumiaki Kojima;J. Kawabe;F. Ushikubi
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作者：
Koh-ichi Yuhki;H. Kashiwagi;Fumiaki Kojima;J. Kawabe;F. Ushikubi
前列腺素类化合物在心血管疾病发病机制和病理状况发展中的作用已经使用缺乏个体、特定前列腺素类受体的小鼠进行了研究。前列腺素 (PG) I2 在急性心肌梗死模型中保护心脏免受缺血再灌注损伤。此外，PGI2 抑制了压力超负荷引起的心脏肥大的发展。除了其强大的血管舒张作用外，PGI2 通过激活肾素-血管紧张素-醛固酮系统，对肾血管性高血压的发生也起到了重要作用。血栓烷 (TX) A2 和 PGF2α 被发现是脂多糖诱导的全身炎症条件下炎症性心动过速的介质。在导致血管低反应状态的脓毒症条件下，TXA2 通过抑制血管平滑肌细胞中诱导型一氧化氮合酶的诱导来维持血管张力。缺乏 PGE2 受体亚型 EP3 的小鼠有出血倾向，并且由于血小板活化缺陷而对血栓栓塞具有抵抗力。从这些研究中，前列腺素类化合物在心血管疾病发病机制中的重要而新颖的作用已经得到阐明。
The roles of prostanoids in the pathogenesis of cardiovascular diseases and in the development of pathological conditions have been examined using mice lacking the individual, specific prostanoid receptor. Prostaglandin (PG) I2 protected the heart from ischemia-reperfusion injury in a model of acute myocardial infarction. In addition, PGI2 suppressed the development of pressure overload-induced cardiac hypertrophy. Aside from its potent vasodilatory action, PGI2 contributed critically to the development of renovascular hypertension via the activation of the renin-angiotensin-aldosterone system. Thromboxane (TX) A2 and PGF2alpha were found to be the mediators of inflammatory tachycardia under a systemic inflammatory condition induced by lipopolysaccharide. Under a septic condition leading to a vascular hypo-responsive state, TXA2 worked to maintain vascular tone by inhibiting the induction of inducible nitric oxide synthase in vascular smooth muscle cells. Mice lacking the PGE2 receptor subtype EP3 had a bleeding tendency and were resistant to thromboembolism, due to a defective activation of platelets. From these studies, the important and novel roles of prostanoids in the pathogenesis of cardiovascular diseases have been clarified.