Angiotensin-(1-7) attenuates angiotensin II-induced cardiac remodeling associated with upregulation of dual-specificity phosphatase 1
Angiotensin-(1-7) attenuates angiotensin II-induced cardiac remodeling associated with upregulation of dual-specificity phosphatase 1
复制标题
DOI：
10.1152/ajpheart.00908.2011
复制
发表时间：
2012-02-01
影响因子：
4.8
通讯作者：
Tallant, E. Ann
中科院分区：
文献类型：
--
作者：
McCollum, LaTronya T.;Gallagher, Patricia E.;Tallant, E. Ann
麦科勒姆LT，加拉格尔体育，塔兰特EA。血管紧张素-(1-7)减轻血管紧张素II诱导的心脏重构，与双特异性磷酸酶1上调相关。AM J Physiol心脏环Physiol 302：H801-H810,2012。2011年12月2日首次出版；DOI：10.1152/ajpheart.00908.2011。-慢性高血压通过血流动力学和体液因素的组合诱导心脏重构，包括左心室肥厚和纤维化。在以前的研究中，我们发现七肽Ang-(1-7)通过降低MAPKs ERK1和ERK2的活性来抑制丝裂原刺激的体外培养的心肌细胞的生长。在本研究中，应用Ang-(1-7)对生理盐水或Ang II灌流的大鼠进行治疗，以确定七肽是否能减少体内心肌细胞的肥大，并确定参与这一过程的信号通路。血管紧张素转换酶II使正常血压大鼠的收缩压升高50毫米汞柱，并伴随着心肌细胞横截面积、心房利钠肽和脑利钠肽mRNA的增加。虽然Ang-(1-7)对Ang II刺激的血压升高无影响，但七肽激素显著降低Ang II介导的心肌细胞横截面积、间质纤维化和利钠肽mRNAs的增加。Ang II增加了磷酸化ERK1和磷酸化ERK2，而Ang-(1-7)共同处理降低了这两个MAPK的磷酸化。Ang II和Ang-(1-7)均不改变ERK1/2 MAPK激酶MEK1/2。然而，Ang-(1-7)与Ang II一起或不与Ang II一起输注，均可增加MAPK双特异性磷酸酶(DUSP)-1；相反，Ang-(1-7)对DUSP-1无影响，提示Ang-(1-7)上调DUSP-1以减少Ang II刺激的ERK激活。这些结果表明，Ang-(1-7)可减轻与慢性血压升高和MAPK磷酸酶上调相关的心脏重塑，并可能对高血压患者具有心脏保护作用。
McCollum LT, Gallagher PE, Tallant EA. Angiotensin-(1-7) attenuates angiotensin II-induced cardiac remodeling associated with upregulation of dual-specificity phosphatase 1. Am J Physiol Heart Circ Physiol 302: H801-H810, 2012. First published December 2, 2011; doi:10.1152/ajpheart.00908.2011.-Chronic hypertension induces cardiac remodeling, including left ventricular hypertrophy and fibrosis, through a combination of both hemodynamic and humoral factors. In previous studies, we showed that the heptapeptide ANG-(1-7) prevented mitogen-stimulated growth of cardiac myocytes in vitro, through a reduction in the activity of the MAPKs ERK1 and ERK2. In this study, saline-or ANG II-infused rats were treated with ANG-(1-7) to determine whether the heptapeptide reduces myocyte hypertrophy in vivo and to identify the signaling pathways involved in the process. ANG II infusion into normotensive rats elevated systolic blood pressure >50 mmHg, in association with increased myocyte cross-sectional area, ventricular atrial natriuretic peptide mRNA, and ventricular brain natriuretric peptide mRNA. Although infusion with ANG-(1-7) had no effect on the ANG II-stimulated elevation in blood pressure, the heptapeptide hormone significantly reduced the ANG II-mediated increase in myocyte cross-sectional area, interstitial fibrosis, and natriuretic peptide mRNAs. ANG II increased phosphoERK1 and phospho-ERK2, whereas cotreatment with ANG-(1-7) reduced the phosphorylation of both MAPKs. Neither ANG II nor ANG-(1-7) altered the ERK1/2 MAPK kinase MEK1/2. However, ANG-(1-7) infusion, with or without ANG II, increased the MAPK phosphatase dual-specificity phosphatase (DUSP)-1; in contrast, treatment with ANG II had no effect on DUSP-1, suggesting that ANG-(1-7) upregulates DUSP-1 to reduce ANG II-stimulated ERK activation. These results indicate that ANG-(1-7) attenuates cardiac remodeling associated with a chronic elevation in blood pressure and upregulation of a MAPK phosphatase and may be cardioprotective in patients with hypertension.