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Loss of Apelin Augments Angiotensin II-Induced Cardiac Dysfunction and Pathological Remodeling

Apelin is an inotropic and cardioprotective peptide that exhibits beneficial effects through activation of the APJ receptor in the pathology of cardiovascular diseases. Apelin induces the expression of angiotensin-converting enzyme 2 (ACE2) in failing hearts, thereby improving heart function in an a...

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Autores principales: Sato, Teruki, Kadowaki, Ayumi, Suzuki, Takashi, Ito, Hiroshi, Watanabe, Hiroyuki, Imai, Yumiko, Kuba, Keiji
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6358887/
https://www.ncbi.nlm.nih.gov/pubmed/30634441
http://dx.doi.org/10.3390/ijms20020239
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author Sato, Teruki
Kadowaki, Ayumi
Suzuki, Takashi
Ito, Hiroshi
Watanabe, Hiroyuki
Imai, Yumiko
Kuba, Keiji
author_facet Sato, Teruki
Kadowaki, Ayumi
Suzuki, Takashi
Ito, Hiroshi
Watanabe, Hiroyuki
Imai, Yumiko
Kuba, Keiji
author_sort Sato, Teruki
collection PubMed
description Apelin is an inotropic and cardioprotective peptide that exhibits beneficial effects through activation of the APJ receptor in the pathology of cardiovascular diseases. Apelin induces the expression of angiotensin-converting enzyme 2 (ACE2) in failing hearts, thereby improving heart function in an angiotensin 1–7-dependent manner. Whether apelin antagonizes the over-activation of the renin–angiotensin system in the heart remains elusive. In this study we show that the detrimental effects of angiotensin II (Ang II) were exacerbated in the hearts of aged apelin-gene-deficient mice. Ang II-mediated cardiac dysfunction and hypertrophy were augmented in apelin knockout mice. The loss of apelin increased the ratio of angiotensin-converting enzyme (ACE) to ACE2 expression in the Ang II-stressed hearts, and Ang II-induced cardiac fibrosis was markedly enhanced in apelin knockout mice. mRNA expression of pro-fibrotic genes, such as transforming growth-factor beta (TGF-β) signaling, were significantly upregulated in apelin knockout hearts. Consistently, treatment with the ACE-inhibitor Captopril decreased cardiac contractility in apelin knockout mice. In vitro, apelin ameliorated Ang II-induced TGF-β expression in primary cardiomyocytes, accompanied with reduced hypertrophy. These results provide direct evidence that endogenous apelin plays a crucial role in suppressing Ang II-induced cardiac dysfunction and pathological remodeling.
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spelling pubmed-63588872019-02-06 Loss of Apelin Augments Angiotensin II-Induced Cardiac Dysfunction and Pathological Remodeling Sato, Teruki Kadowaki, Ayumi Suzuki, Takashi Ito, Hiroshi Watanabe, Hiroyuki Imai, Yumiko Kuba, Keiji Int J Mol Sci Article Apelin is an inotropic and cardioprotective peptide that exhibits beneficial effects through activation of the APJ receptor in the pathology of cardiovascular diseases. Apelin induces the expression of angiotensin-converting enzyme 2 (ACE2) in failing hearts, thereby improving heart function in an angiotensin 1–7-dependent manner. Whether apelin antagonizes the over-activation of the renin–angiotensin system in the heart remains elusive. In this study we show that the detrimental effects of angiotensin II (Ang II) were exacerbated in the hearts of aged apelin-gene-deficient mice. Ang II-mediated cardiac dysfunction and hypertrophy were augmented in apelin knockout mice. The loss of apelin increased the ratio of angiotensin-converting enzyme (ACE) to ACE2 expression in the Ang II-stressed hearts, and Ang II-induced cardiac fibrosis was markedly enhanced in apelin knockout mice. mRNA expression of pro-fibrotic genes, such as transforming growth-factor beta (TGF-β) signaling, were significantly upregulated in apelin knockout hearts. Consistently, treatment with the ACE-inhibitor Captopril decreased cardiac contractility in apelin knockout mice. In vitro, apelin ameliorated Ang II-induced TGF-β expression in primary cardiomyocytes, accompanied with reduced hypertrophy. These results provide direct evidence that endogenous apelin plays a crucial role in suppressing Ang II-induced cardiac dysfunction and pathological remodeling. MDPI 2019-01-09 /pmc/articles/PMC6358887/ /pubmed/30634441 http://dx.doi.org/10.3390/ijms20020239 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sato, Teruki
Kadowaki, Ayumi
Suzuki, Takashi
Ito, Hiroshi
Watanabe, Hiroyuki
Imai, Yumiko
Kuba, Keiji
Loss of Apelin Augments Angiotensin II-Induced Cardiac Dysfunction and Pathological Remodeling
title Loss of Apelin Augments Angiotensin II-Induced Cardiac Dysfunction and Pathological Remodeling
title_full Loss of Apelin Augments Angiotensin II-Induced Cardiac Dysfunction and Pathological Remodeling
title_fullStr Loss of Apelin Augments Angiotensin II-Induced Cardiac Dysfunction and Pathological Remodeling
title_full_unstemmed Loss of Apelin Augments Angiotensin II-Induced Cardiac Dysfunction and Pathological Remodeling
title_short Loss of Apelin Augments Angiotensin II-Induced Cardiac Dysfunction and Pathological Remodeling
title_sort loss of apelin augments angiotensin ii-induced cardiac dysfunction and pathological remodeling
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6358887/
https://www.ncbi.nlm.nih.gov/pubmed/30634441
http://dx.doi.org/10.3390/ijms20020239
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