Increased expression of adrenomedullin 2/intermedin in rat hearts with congestive heart failure

被引：38
作者：
Hirose, Takuo [1 ]
Totsune, Kazuhito [1 ,2 ]
Mori, Nobuyoshi [3 ]
Morimoto, Ryo [4 ]
Hashimoto, Masahiro [1 ]
Nakashige, Yukiko [1 ]
Metoki, Hirohito [1 ,5 ]
Asayama, Kei [2 ]
Kikuya, Masahiro [1 ]
Ohkubo, Takayoshi [2 ,6 ]
Hashimoto, Junichiro [2 ,6 ]
Sasano, Hironobu [7 ]
Kohzuki, Masahiro [3 ]
Takahashi, Kazzuhiro [2 ,8 ]
Imai, Yutaka [1 ,2 ]
机构：
[1] Tohoku Univ, Grad Sch Pharmaceut Sci & Med, Dept Clin Pharmacol & Therapeut, Aoba Ku, Sendai, Miyagi 9808578, Japan
[2] Tohoku Univ, 21st Ctr Excellence Program, Comprehens Res & Educ Ctr Planning Drug Dev & Cli, Aoba Ku, Sendai, Miyagi 9808578, Japan
[3] Tohoku Univ, Sch Med, Dept Internal Med & Rehabil Sci, Aoba Ku, Sendai, Miyagi 9808574, Japan
[4] Tohoku Univ, Sch Med, Dept Med, Aoba Ku, Sendai, Miyagi 9808574, Japan
[5] Tohoku Univ, Sch Med, Dept Med Genet, Aoba Ku, Sendai, Miyagi 9808574, Japan
[6] Tohoku Univ, Grad Sch Pharmaceut Sci & Med, Dept Planning Drug Dev & Clin Evaluat, Aoba Ku, Sendai, Miyagi 9808575, Japan
[7] Tohoku Univ, Sch Med, Dept Pathol, Aoba Ku, Sendai, Miyagi 9808574, Japan
[8] Tohoku Univ, Grad Sch Med, Dept Endocrinol & Appl Med Sci, Aoba Ku, Sendai, Miyagi 9808575, Japan
来源：
EUROPEAN JOURNAL OF HEART FAILURE | 2008年 / 10卷 / 09期
关键词：
Adrenomedullin; 2/Intermedin; Heart failure; RT-PCR; Immunohistochemistry;
D O I：
10.1016/j.ejheart.2008.06.020
中图分类号：
R5 [内科学];
学科分类号：
1002 ; 100201 ;
摘要：
Adrenomedullin 2/intermedin (AM2/IMD) is a novel member of the calcitonin/calcitonin gene-related peptide family. To investigate the pathophysiological role of AM2/IMD in heart failure, we examined the expression of AM2/IMD, adrenomedullin (AM) and receptor complex components (calcitonin receptor-like receptor, three types of receptor activity-modifying proteins) by quantitative RT-PCR and immunohistochemistry in the hearts and kidneys of rats with congestive heart failure (CHF). Significantly increased levels of AM2/IMD mRNA were found in the atrium, right ventricle, non-infarcted part of the left ventricle and the infarcted part of the left ventricle of CHF rats, compared with sham operated rats (about 2.8-fold, 1.7-fold, 1.7-fold and 2.5-fold, respectively). Expression levels of mRNA encoding AM and the receptor complex components were also increased in the hearts of CHF rats. In a separate experiment, AM2/IMD mRNA levels in the heart did not differ between Wistar-Kyoto and spontaneously hypertensive rats. In both sham operated and CHF rats, the myocardium was diffusely immunostained with AM2/IMD. The fibrotic infarcted layer was not immunostained with AM2/IMD but was surrounded by positively immunostained myocardial layers. These findings suggest that the expression of AM2/IMD is enhanced in the failing heart, and AM2/IMD has a certain pathophysiological role in heart failure. (C) 2008 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码：840 / 849
页数：10
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