The Key Laboratory of Remodeling-related Cardiovascular Diseases, Department of Pathology School of Basic Medical Sciences, Capital Medical University, Beijing, China.
Peptides. 2011 Oct;32(10):2108-15. doi: 10.1016/j.peptides.2011.09.015. Epub 2011 Sep 22.
Angiotensin II (Ang II) is an important regulator of cardiac function and injury in hypertension. The novel Ang IV peptide/AT4 receptor system has been implicated in several physiological functions and has some effects opposite to those of Ang II. However, little is known about the role of this system in Ang II-induced cardiac injury. Here we studied the effect of Ang IV on Ang II-induced cardiac dysfunction and injury using isolated rat hearts, neonatal cardiomyocytes and cardiac fibroblasts. We found that Ang IV significantly improved Ang II-induced cardiac dysfunction and injury in the isolated heart in response to ischemia/reperfusion (I/R). Moreover, Ang IV inhibited Ang II-induced cardiac cell apoptosis, cardiomyocyte hypertrophy, and proliferation and collagen synthesis of cardiac fibroblasts; these effects were mediated through the AT4 receptor as confirmed by siRNA knockdown. These findings suggest that Ang IV may have a protective effect on Ang II-induced cardiac injury and dysfunction and may be a novel therapeutic target for hypertensive heart disease.
血管紧张素 II（Ang II）是高血压中心脏功能和损伤的重要调节剂。新型血管紧张素 IV 肽/AT4 受体系统与多种生理功能有关，并且具有与 Ang II 相反的作用。但是，关于该系统在 Ang II 诱导的心脏损伤中的作用知之甚少。在这里，我们使用分离的大鼠心脏、乳鼠心肌细胞和心肌成纤维细胞研究了 Ang IV 对 Ang II 诱导的心脏功能障碍和损伤的影响。我们发现 Ang IV 可显著改善分离心脏对缺血/再灌注（I / R）的 Ang II 诱导的心脏功能障碍和损伤。此外，Ang IV 抑制 Ang II 诱导的心肌细胞凋亡、心肌细胞肥大以及心肌成纤维细胞的增殖和胶原合成；这些作用是通过 siRNA 敲低证实的 AT4 受体介导的。这些发现表明 Ang IV 可能对 Ang II 诱导的心脏损伤和功能障碍具有保护作用，并且可能是高血压性心脏病的新的治疗靶标。
