Cardiac dopamine D1 receptor triggers ventricular arrhythmia in chronic heart failure

Yamaguchi, Toshihiro; Sumida, Tomokazu; Nomura, Seitaro; Satoh, Masahiro; Higo, Tomoaki; Ito, Masamichi; Ko, Toshiyuki; Fujita, Kanna; Sweet, Mary E.; Sanbe, Atsushi; Yoshimi, Kenji; Manabe, Ichiro; Sasaoka, Toshikuni; Taylor, Matthew R. G.; Toko, Haruhiro; Takimoto, Eiki; Naito, Atsuhiko T.; Komuro, Issei

doi:10.1038/s41467-020-18128-x

Cited by 56 publications

(42 citation statements)

References 45 publications

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“…Western blotting was performed as previously described 53 . Tissues and cells were homogenized in ice-cold RIPA buffer containing protease inhibitor (cOmplete Protease Inhibitor Cocktail, Merck) and phosphatase inhibitor (PhosSTOP, Sigma).…”

Section: Methodsmentioning

confidence: 99%

CXCR7 ameliorates myocardial infarction as a β-arrestin-biased receptor

Ishizuka

Harada

Nomura

et al. 2021

Sci Rep

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Most seven transmembrane receptors (7TMRs) are G protein-coupled receptors; however, some 7TMRs evoke intracellular signals through β-arrestin as a biased receptor. As several β-arrestin-biased agonists have been reported to be cardioprotective, we examined the role of the chemokine receptor CXCR7 as a β-arrestin-biased receptor in the heart. Among 510 7TMR genes examined, Cxcr7 was the most abundantly expressed in the murine heart. Single-cell RNA-sequencing analysis revealed that Cxcr7 was abundantly expressed in cardiomyocytes and fibroblasts. Cardiomyocyte-specific Cxcr7 null mice showed more prominent cardiac dilatation and dysfunction than control mice 4 weeks after myocardial infarction. In contrast, there was no difference in cardiac phenotypes between fibroblast-specific Cxcr7-knockout mice and control mice even after myocardial infarction. TC14012, a specific agonist of CXCR7, significantly recruited β-arrestin to CXCR7 in CXCR7-expressing cells and activated extracellular signal-regulated kinase (ERK) in neonatal rat cardiomyocytes. Cxcr7 expression was significantly increased and ERK was activated in the border zone of the heart in control, but not Cxcr7 null mice. These results indicate that the abundantly expressed CXCR7 in cardiomyocytes may play a protective role in the heart as a β-arrestin-biased receptor and that CXCR7 may be a novel therapeutic target for myocardial infarction.

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Section: Methodsmentioning

confidence: 99%

CXCR7 ameliorates myocardial infarction as a β-arrestin-biased receptor

Ishizuka

Harada

Nomura

et al. 2021

Sci Rep

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“…DA receptors are expressed in the heart ( 39 , 40 ), but the source of DA is not clear. One possible hypothesis is that sympathetic noradrenergic neurons release DA.…”

Section: Discussionmentioning

confidence: 99%

Tyrosine hydroxylase conditional KO mice reveal peripheral tissue-dependent differences in dopamine biosynthetic pathways

Miyajima

Kawamoto²,

Hara³

et al. 2021

Journal of Biological Chemistry

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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“…More specifically, evidence has shown that dysfunction in the D3R signaling system is associated with an increase in blood pressure in mice ( 14 , 15 ). Emerging evidence suggests the existence of an intracardiac dopaminergic system plays a role in regulating cardiac function, mainly mediated by the dopamine receptor subtypes D1 and D3 ( 16 , 17 ). In particular, the global loss of D3R function has been shown to negatively impact cardiac function and exacerbate the progression of fibrosis in mice ( 16 ).…”

Section: Introductionmentioning

confidence: 99%

Loss of Function in Dopamine D3 Receptor Attenuates Left Ventricular Cardiac Fibroblast Migration and Proliferation in vitro

Kisling

Byrne

Parekh

et al. 2021

Front. Cardiovasc. Med.

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Evidence suggests the existence of an intracardiac dopaminergic system that plays a pivotal role in regulating cardiac function and fibrosis through G-protein coupled receptors, particularly mediated by dopamine receptor 3 (D3R). However, the expression of dopamine receptors in cardiac tissue and their role in cardiac fibroblast function is unclear. In this brief report, first we determined expression of D1R and D3R both in left ventricle (LV) tissue and fibroblasts. Then, we explored the role of D3R in the proliferation and migration of fibroblast cell cultures using both genetic and pharmaceutical approaches; specifically, we compared cardiac fibroblasts isolated from LV of wild type (WT) and D3R knockout (D3KO) mice in response to D3R-specific pharmacological agents. Finally, we determined if loss of D3R function could significantly alter LV fibroblast expression of collagen types I (Col1a1) and III (Col3a1). Cardiac fibroblast proliferation was attenuated in D3KO cells, mimicking the behavior of WT cardiac fibroblasts treated with D3R antagonist. In response to scratch injury, WT cardiac fibroblasts treated with the D3R agonist, pramipexole, displayed enhanced migration compared to control WT and D3KO cells. Loss of function in D3R resulted in attenuation of both proliferation and migration in response to scratch injury, and significantly increased the expression of Col3a1 in LV fibroblasts. These findings suggest that D3R may mediate cardiac fibroblast function during the wound healing response. To our knowledge this is the first report of D3R's expression and functional significance directly in mouse cardiac fibroblasts.

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Cardiac dopamine D1 receptor triggers ventricular arrhythmia in chronic heart failure

Cited by 56 publications

References 45 publications

CXCR7 ameliorates myocardial infarction as a β-arrestin-biased receptor

CXCR7 ameliorates myocardial infarction as a β-arrestin-biased receptor

Tyrosine hydroxylase conditional KO mice reveal peripheral tissue-dependent differences in dopamine biosynthetic pathways

Loss of Function in Dopamine D3 Receptor Attenuates Left Ventricular Cardiac Fibroblast Migration and Proliferation in vitro

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