The effect of Intermedin on Angiotensin II and Endothelin-1 Induced Ventricular Myocyte Hypertrophy in Neonatal Rat
The effect of Intermedin on Angiotensin II and Endothelin-1 Induced Ventricular Myocyte Hypertrophy in Neonatal Rat
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Intermedin对血管紧张素II和内皮素1诱导的新生大鼠心室肌细胞肥大的影响
DOI：
10.7754/clin.lab.2012.120708
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发表时间：
2013-01-01
影响因子：
0.7
通讯作者：
He, Sen
中科院分区：
文献类型：
--
作者：
Liu, Kai;Deng, Xiaoming;He, Sen
背景资料：中间肽（IMD）是降钙素基因相关肽（CGRP）和肾上腺髓质素（ADM）的一种新的多肽，可能具有局部的心功能调节作用。本研究旨在探讨IMD对血管紧张素II（Ang II）和内皮素-1（ET-1）诱导的新生大鼠心室肌细胞肥大的影响，并探讨其可能的作用机制。新生大鼠心肌细胞培养在无血清培养基中有和没有血管紧张素Ⅱ（1 μ mol/L）或ET-1（60 μ mol/L）的IMD（1 μ mol/L）的存在和不存在。肥大反应（包括细胞表面积、α-肌动蛋白和β-肌球蛋白重链mRNA表达）和心肌细胞NADPH氧化酶gp 91 phox的表达。血管紧张素II诱导心肌细胞大小增加至305 +/- 32 μ m（2）（n = 198，p < 0.05，48小时），α-肌动蛋白表达增加到4 +/- 2.8倍（n = 6，p < 0.05，48小时），P-肌球蛋白重链表达增加到11 +/- 4.8倍（n = 6，p < 0.05，在48小时），NADPH氧化酶的gp 91 phox亚基的表达达到29.4 +/-12.7倍（n = 6，p < 0.05，在48小时）。这些效应均被IMD显著抑制;心肌细胞大小、α-肌动蛋白表达、β-肌球蛋白重链表达和gp 91 phox表达减少至265 ± 32 μ m（2）。（n = 374，p < 0.05）、3.0 +/-1.7-倍（n = 6，p < 0.05）、8.7 +/-4.9-倍（n = 6，p < 0.05）、3.9 +/-3-倍（n = 6，p < 0.05）。IMD也显着抑制ET 1诱导的心肌细胞大小和超氧化物generation.Conclusions的增加：IMD对新生儿心肌细胞的抗肥大作用，通过减少超氧化物的水平，这表明抗氧化作用有助于IMD的抗肥大作用。
Background: Intermedin (IMD), a novel peptide related to calcitonin gene-related peptide (CGRP) and adrenomedullin (ADM), may have localized actions as a modulator of cardiac function. The aim of the study is to explore the effect of IMD on angiotensin II (Ang II) and endothelin-1 (ET-1) induced hypertrophy in ventricular myocytes of neonatal rat and to try to elucidate the possible mechanism.Methods: Neonatal rat cardiomyocytes were cultured in serum-free medium with and without AngII (1 mu mol/L) or ET-1 (60 mu mol/L) in the presence and absence of IMD (1 mu mol/L). Hypertrophic responses (including cell surface area, alpha-actin, and beta-myosin heavy chain mRNA expression) and cardiomyocyte expression of NADPH oxidase gp91phox were determined.Results: Ang II induced increases in cardiomyocyte size to 305 +/- 32 mu m(2) (n = 198, p < 0.05, at 48 hours), alpha-actin expression to 4 +/- 2.8-fold (n = 6, p < 0.05, at 48 hours) and P-myosin heavy chain expression to 11 +/- 4.8-fold (n = 6, p < 0.05, at 48 hours), and expression of the gp91phox subunit of NADPH oxidase to 29.4 +/- 12.7-fold (n = 6, p < 0.05, at 48 hours). These effects were all significantly inhibited by IMD; cardiomyocyte size, alpha-actin expression, beta-myosin heavy chain expression, and gp91phox expression were reduced to 265 32 mu m(2) (n = 374, p < 0.05), 3.0 +/- 1.7-fold (n = 6, p < 0.05), 8.7 +/- 4.9-fold (n = 6, p < 0.05), 3.9 +/- 3-fold (n = 6, p < 0.05), respectively. IMD also significantly inhibited ET1-induced increases in cardiomyocyte size and superoxide generation.Conclusions: IMD exerts an antihypertrophic effect on neonatal cardiomyocytes by reduced levels of superoxide, suggesting that an antioxidant action contributes to the antihypertrophic actions of IMD.