Department of Medicine, Monash University, Alfred Hospital, Victoria, Australia.
Peptides. 2010 Aug;31(8):1523-30. doi: 10.1016/j.peptides.2010.04.026. Epub 2010 May 7.
Urotensin II (UII) is a potential mediator in the pathogenesis of cardiovascular disease, and inhibition of its actions at the urotensin receptor (UT) has been shown to improve cardiac function and structural changes of the myocardium in a model of myocardial infarction. In this study we utilized a model of pressure-overload hypertrophy induced by abdominal aortic constriction (AAC) which resulted in hypertrophy, increased fibrosis and impaired diastolic and systolic function. These changes were associated with a 4-fold increase in UII protein expression in the myocardium. Treatment of animals with a selective UT (SB-657510) antagonist for 20 weeks at a dose of 1500 ppm did not improve cardiac function as assessed by echocardiography and pressure-volume loop analysis, nor did it inhibit left ventricular hypertrophy or fibrosis. We hypothesize that other neurohumoral pathways may have a greater involvement in the pathogenesis of this model. Targeting the UII system appears to be insufficient to observe a beneficial outcome.
尾加压素 II（UII）是心血管疾病发病机制中的一种潜在介质，其在尾加压素受体（UT）上的作用被抑制已被证明可改善心肌梗死后的心脏功能和心肌结构变化。在这项研究中，我们利用腹主动脉缩窄（AAC）引起的压力超负荷肥大模型，该模型导致肥大、纤维化增加以及舒张和收缩功能受损。这些变化与心肌中 UII 蛋白表达增加 4 倍有关。用选择性 UT（SB-657510）拮抗剂以 1500ppm 的剂量治疗 20 周，并未改善超声心动图和压力-容积环分析评估的心脏功能，也未抑制左心室肥大或纤维化。我们假设其他神经激素途径可能在该模型的发病机制中具有更大的作用。靶向 UII 系统似乎不足以观察到有益的结果。
