Evidence of a novel intracrine mechanism in angiotensin II-induced cardiac hypertrophy
Evidence of a novel intracrine mechanism in angiotensin II-induced cardiac hypertrophy
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DOI：
10.1016/j.regpep.2004.04.004
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发表时间：
2004-08-15
影响因子：
--
通讯作者：
Kumar, R
中科院分区：
文献类型：
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作者：
Baker, KM;Chernin, MI;Kumar, R
血管紧张素II （angii）通过与质膜AT受体结合，通过体液、自分泌和旁分泌途径调节心脏稳态。最近的文献证明，在一些细胞系中，Ang II的胞内生长作用并不涉及与质膜受体的相互作用。我们假设这种内分泌机制在心脏中起作用，并可能参与Ang II诱导的心脏肥厚。构建腺病毒载体和质粒载体在细胞内表达Ang II肽。腺病毒载体感染的新生大鼠心室肌细胞（nrvm）通过细胞大小、蛋白质合成和增强的细胞骨架排列显示出显著的肥厚生长。注射质粒载体的成年小鼠在48小时后出现明显的心脏肥大，血压和血浆Ang II水平均未升高。这伴随着转化生长因子- β (tgf - β)和胰岛素样生长因子-1 （IGF-1）基因转录的增加。排除细胞外Ang II和质膜AT(1)受体的参与，氯沙坦没有阻断生长效应。这些数据表明了一种以前未知的Ang II在心脏中的生长机制，在设计阻断Ang II作用的治疗策略时应考虑到这一点。(C) 2004 Elsevier B.V.版权所有
Angiotensin II (Ang II) has a significant role in regulating cardiac homeostasis through humoral, autocrine and paracrine pathways, via binding to the plasma membrane AT, receptor. Recent literature has provided evidence for intracrine growth effects of Ang II in some cell lines, which does not involve interaction with the plasma membrane receptor. We hypothesized that such intracrine mechanisms are operative in the heart and likely participate in the cardiac hypertrophy induced by Ang II. Adenoviral and plasmid vectors were constructed to express Ang II peptide intracellularly. Neonatal rat ventricular myocytes (NRVMs) infected with the adenoviral vector showed significant hypertrophic growth as determined by cell size, protein synthesis and enhanced cytoskeletal arrangement. Adult mice injected with the plasmid vector developed significant cardiac hypertrophy after 48 h, without an increase in blood pressure or plasma Ang II levels. This was accompanied by increased transcription of transforming growth factor-beta (TGF-beta) and insulin-like growth factor-1 (IGF-1) genes. Losartan did not block the growth effects, excluding the involvement of extracellular Ang II and the plasma membrane AT(1) receptor. These data demonstrate a previously unknown growth mechanism of Ang II in the heart, which should be considered when designing therapeutic strategies to block Ang II actions. (C) 2004 Elsevier B.V. All rights reserved.