Role of brain serotonin dysfunction in the pathophysiology of congestive heart failure

Lei Li, Sachio Morimoto, Sachiko Take, Dong Yun Zhan, Cheng Kun Du, Yuan Yuan Wang, Xue Li Fan, Tatsuya Yoshihara, Fumi Takahashi-Yanaga, Toshihiko Katafuchi, Toshiyuki Sasaguri

研究成果: ジャーナルへの寄稿記事

5 引用 (Scopus)

抄録

Inherited or non-inherited dilated cardiomyopathy (DCM) patients develop varied disease phenotypes leading to death after developing congestive heart failure (HF) or sudden death with mild or no overt HF symptoms, suggesting that environmental and/or genetic factors may modify the disease phenotype of DCM. In this study, we sought to explore unknown genetic factors affecting the disease phenotype of monogenic inherited human DCM. Knock-in mice bearing a sarcomeric protein mutation that causes DCM were created on different genetic backgrounds; BALB/c and C57Bl/6. DCM mice on the BALB/c background showed cardiac enlargement and systolic dysfunction and developed congestive HF before died. In contrast, DCM mice on the C57Bl/6 background developed no overt HF symptoms and died suddenly, although they showed considerable cardiac enlargement and systolic dysfunction. BALB/c mice have brain serotonin dysfunction due to a single nucleotide polymorphism (SNP) in tryptophan hydroxylase 2 (TPH2). Brain serotonin dysfunction plays a critical role in depression and anxiety and BALB/c mice exhibit depression- and anxiety-related behaviors. Since depression is common and associated with poor prognosis in HF patients, we examined therapeutic effects of anti-depression drug paroxetine and anti-anxiety drug buspirone that could improve the brain serotonin function in mice. Both drugs reduced cardiac enlargement and improved systolic dysfunction and symptoms of severe congestive HF in DCM mice on the BALB/c background. These results strongly suggest that genetic backgrounds involving brain serotonin dysfunction, such as TPH2 gene SNP, may play an important role in the development of congestive HF in DCM.

元の言語英語
ページ(範囲)760-767
ページ数8
ジャーナルJournal of Molecular and Cellular Cardiology
53
発行部数6
DOI
出版物ステータス出版済み - 12 1 2012

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Dilated Cardiomyopathy
Serotonin
Heart Failure
Brain
Depression
Tryptophan Hydroxylase
Phenotype
Single Nucleotide Polymorphism
Anxiety
Buspirone
Paroxetine
Anti-Anxiety Agents
Therapeutic Uses
Sudden Death
Pharmaceutical Preparations
Mutation
Genes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

これを引用

Role of brain serotonin dysfunction in the pathophysiology of congestive heart failure. / Li, Lei; Morimoto, Sachio; Take, Sachiko; Zhan, Dong Yun; Du, Cheng Kun; Wang, Yuan Yuan; Fan, Xue Li; Yoshihara, Tatsuya; Takahashi-Yanaga, Fumi; Katafuchi, Toshihiko; Sasaguri, Toshiyuki.

:: Journal of Molecular and Cellular Cardiology, 巻 53, 番号 6, 01.12.2012, p. 760-767.

研究成果: ジャーナルへの寄稿記事

Li, L, Morimoto, S, Take, S, Zhan, DY, Du, CK, Wang, YY, Fan, XL, Yoshihara, T, Takahashi-Yanaga, F, Katafuchi, T & Sasaguri, T 2012, 'Role of brain serotonin dysfunction in the pathophysiology of congestive heart failure', Journal of Molecular and Cellular Cardiology, 巻. 53, 番号 6, pp. 760-767. https://doi.org/10.1016/j.yjmcc.2012.08.006
Li, Lei ; Morimoto, Sachio ; Take, Sachiko ; Zhan, Dong Yun ; Du, Cheng Kun ; Wang, Yuan Yuan ; Fan, Xue Li ; Yoshihara, Tatsuya ; Takahashi-Yanaga, Fumi ; Katafuchi, Toshihiko ; Sasaguri, Toshiyuki. / Role of brain serotonin dysfunction in the pathophysiology of congestive heart failure. :: Journal of Molecular and Cellular Cardiology. 2012 ; 巻 53, 番号 6. pp. 760-767.
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abstract = "Inherited or non-inherited dilated cardiomyopathy (DCM) patients develop varied disease phenotypes leading to death after developing congestive heart failure (HF) or sudden death with mild or no overt HF symptoms, suggesting that environmental and/or genetic factors may modify the disease phenotype of DCM. In this study, we sought to explore unknown genetic factors affecting the disease phenotype of monogenic inherited human DCM. Knock-in mice bearing a sarcomeric protein mutation that causes DCM were created on different genetic backgrounds; BALB/c and C57Bl/6. DCM mice on the BALB/c background showed cardiac enlargement and systolic dysfunction and developed congestive HF before died. In contrast, DCM mice on the C57Bl/6 background developed no overt HF symptoms and died suddenly, although they showed considerable cardiac enlargement and systolic dysfunction. BALB/c mice have brain serotonin dysfunction due to a single nucleotide polymorphism (SNP) in tryptophan hydroxylase 2 (TPH2). Brain serotonin dysfunction plays a critical role in depression and anxiety and BALB/c mice exhibit depression- and anxiety-related behaviors. Since depression is common and associated with poor prognosis in HF patients, we examined therapeutic effects of anti-depression drug paroxetine and anti-anxiety drug buspirone that could improve the brain serotonin function in mice. Both drugs reduced cardiac enlargement and improved systolic dysfunction and symptoms of severe congestive HF in DCM mice on the BALB/c background. These results strongly suggest that genetic backgrounds involving brain serotonin dysfunction, such as TPH2 gene SNP, may play an important role in the development of congestive HF in DCM.",
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AU - Wang, Yuan Yuan

AU - Fan, Xue Li

AU - Yoshihara, Tatsuya

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