Institute of Brain Science, Shanxi Datong University School of Medical Science, Datong, Shanxi, PR China.
J Cardiovasc Pharmacol. 2010 Jul;56(1):45-52. doi: 10.1097/FJC.0b013e3181ddc785.
Intermedin (IMD) is coexpressed in the heart with its receptor, which suggests that it may have localized actions as a modulator of cardiac function. The present study was designed to observe the interaction between IMD and cardiac hypertrophy and the possible mechanism involved in the antihypertrophic effects of IMD1-53 in cultured neonatal ventricular myocytes.
Myocyte hypertrophy was induced by treating the cells with angiotensin II, and the hypertrophic response was characterized by a significant increase in cell surface area, protein synthesis, and BNP mRNA expression.
Our results showed that angiotensin II led to an obvious decrease in the production, secretion, and mRNA expression of IMD and increase receptor activity modifying proteins 1, 3 mRNA expression. Moreover, IMD1-53 inhibited the angiotensin II-induced hypertrophic response and the effects of IMD1-53 were similar to those of equivalent-dose adrenomedullin and could been blocked by H89. Otherwise, in our study, IMD1-53 resulted in dose-dependent increases of cAMP production in cardiomyocytes.
Thus, IMD and its receptor system are involved in cardiac hypertrophy, and like adrenomedullin, IMD1-53 exerts an antihypertrophic effect on neonatal cardiomyocytes and the effect can be mediated by the cAMP/PKA pathway.
中介素（IMD）与心脏中的受体共表达，这表明它可能具有局部作用，作为心脏功能的调节剂。本研究旨在观察 IMD 与心脏肥大的相互作用，以及 IMD1-53 在培养的新生心室肌细胞中抗心肌肥大作用的可能机制。
用血管紧张素 II 处理细胞诱导心肌细胞肥大，通过细胞表面积、蛋白质合成和 BNP mRNA 表达的显著增加来表征肥大反应。
我们的结果表明，血管紧张素 II 导致 IMD 的产生、分泌和 mRNA 表达明显减少，而受体活性修饰蛋白 1、3 mRNA 表达增加。此外，IMD1-53 抑制了血管紧张素 II 诱导的心肌肥大反应，其作用与等效剂量的肾上腺髓质素相似，并可被 H89 阻断。此外，在我们的研究中，IMD1-53 导致心肌细胞中环腺苷酸（cAMP）的产生呈剂量依赖性增加。
因此，IMD 及其受体系统参与了心脏肥大，与肾上腺髓质素一样，IMD1-53 对新生心肌细胞具有抗心肌肥大作用，该作用可通过 cAMP/PKA 途径介导。
