DIOL triterpenes block profibrotic effects of angiotensin II and protect from cardiac hypertrophy.

<h4>Background</h4>The natural triterpenes, erythrodiol and uvaol, exert anti-inflammatory, vasorelaxing and anti-proliferative effects. Angiotensin II is a well-known profibrotic and proliferative agent that participates in the cardiac remodeling associated with different pathological s...

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Autores principales:	Ruben Martín, Maria Miana, Raquel Jurado-López, Ernesto Martínez-Martínez, Nieves Gómez-Hurtado, Carmen Delgado, Maria Visitación Bartolomé, José Alberto San Román, Claudia Cordova, Vicente Lahera, Maria Luisa Nieto, Victoria Cachofeiro
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/31318f08ff3e4b7fa18ce0a62795e37e
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spelling	oai:doaj.org-article:31318f08ff3e4b7fa18ce0a62795e37e2021-11-18T07:11:30ZDIOL triterpenes block profibrotic effects of angiotensin II and protect from cardiac hypertrophy.1932-620310.1371/journal.pone.0041545https://doaj.org/article/31318f08ff3e4b7fa18ce0a62795e37e2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22844495/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>The natural triterpenes, erythrodiol and uvaol, exert anti-inflammatory, vasorelaxing and anti-proliferative effects. Angiotensin II is a well-known profibrotic and proliferative agent that participates in the cardiac remodeling associated with different pathological situations through the stimulation and proliferation of cardiac fibroblasts. Therefore, the aim of the study was to investigate the preventive effects of the natural triterpenes erythrodiol and uvaol on the proliferation and collagen production induced by angiotensin II in cardiac myofibroblasts. Their actions on cardiac hypertrophy triggered by angiotensin II were also studied.<h4>Methodology/principal findings</h4>The effect of erythrodiol and uvaol on angiotensin II-induced proliferation was evaluated in cardiac myofibroblasts from adult rats in the presence or the absence of the inhibitors of PPAR-γ, GW9662 or JNK, SP600125. The effect on collagen levels induced by angiotensin II was evaluated in cardiac myofibroblasts and mouse heart. The presence of low doses of both triterpenes reduced the proliferation of cardiac myofibroblasts induced by angiotensin II. Pretreatment with GW9662 reversed the effect elicited by both triterpenes while SP600125 did not modify it. Both triterpenes at high doses produced an increase in annexing-V binding in the presence or absence of angiotensin II, which was reduced by either SP600125 or GW9662. Erythrodiol and uvaol decreased collagen I and galectin 3 levels induced by angiotensin II in cardiac myofribroblasts. Finally, cardiac hypertrophy, ventricular remodeling, fibrosis, and increases in myocyte area and brain natriuretic peptide levels observed in angiotensin II-infused mice were reduced in triterpene-treated animals.<h4>Conclusions/significance</h4>Erythrodiol and uvaol reduce cardiac hypertrophy and left ventricle remodeling induced by angiotensin II in mice by diminishing fibrosis and myocyte area. They also modulate growth and survival of cardiac myofibroblasts. They inhibit the angiotensin II-induced proliferation in a PPAR-γ-dependent manner, while at high doses they activate pathways of programmed cell death that are dependent on JNK and PPAR-γ.Ruben MartínMaria MianaRaquel Jurado-LópezErnesto Martínez-MartínezNieves Gómez-HurtadoCarmen DelgadoMaria Visitación BartoloméJosé Alberto San RománClaudia CordovaVicente LaheraMaria Luisa NietoVictoria CachofeiroPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 7, p e41545 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ruben Martín Maria Miana Raquel Jurado-López Ernesto Martínez-Martínez Nieves Gómez-Hurtado Carmen Delgado Maria Visitación Bartolomé José Alberto San Román Claudia Cordova Vicente Lahera Maria Luisa Nieto Victoria Cachofeiro DIOL triterpenes block profibrotic effects of angiotensin II and protect from cardiac hypertrophy.
description	<h4>Background</h4>The natural triterpenes, erythrodiol and uvaol, exert anti-inflammatory, vasorelaxing and anti-proliferative effects. Angiotensin II is a well-known profibrotic and proliferative agent that participates in the cardiac remodeling associated with different pathological situations through the stimulation and proliferation of cardiac fibroblasts. Therefore, the aim of the study was to investigate the preventive effects of the natural triterpenes erythrodiol and uvaol on the proliferation and collagen production induced by angiotensin II in cardiac myofibroblasts. Their actions on cardiac hypertrophy triggered by angiotensin II were also studied.<h4>Methodology/principal findings</h4>The effect of erythrodiol and uvaol on angiotensin II-induced proliferation was evaluated in cardiac myofibroblasts from adult rats in the presence or the absence of the inhibitors of PPAR-γ, GW9662 or JNK, SP600125. The effect on collagen levels induced by angiotensin II was evaluated in cardiac myofibroblasts and mouse heart. The presence of low doses of both triterpenes reduced the proliferation of cardiac myofibroblasts induced by angiotensin II. Pretreatment with GW9662 reversed the effect elicited by both triterpenes while SP600125 did not modify it. Both triterpenes at high doses produced an increase in annexing-V binding in the presence or absence of angiotensin II, which was reduced by either SP600125 or GW9662. Erythrodiol and uvaol decreased collagen I and galectin 3 levels induced by angiotensin II in cardiac myofribroblasts. Finally, cardiac hypertrophy, ventricular remodeling, fibrosis, and increases in myocyte area and brain natriuretic peptide levels observed in angiotensin II-infused mice were reduced in triterpene-treated animals.<h4>Conclusions/significance</h4>Erythrodiol and uvaol reduce cardiac hypertrophy and left ventricle remodeling induced by angiotensin II in mice by diminishing fibrosis and myocyte area. They also modulate growth and survival of cardiac myofibroblasts. They inhibit the angiotensin II-induced proliferation in a PPAR-γ-dependent manner, while at high doses they activate pathways of programmed cell death that are dependent on JNK and PPAR-γ.
format	article
author	Ruben Martín Maria Miana Raquel Jurado-López Ernesto Martínez-Martínez Nieves Gómez-Hurtado Carmen Delgado Maria Visitación Bartolomé José Alberto San Román Claudia Cordova Vicente Lahera Maria Luisa Nieto Victoria Cachofeiro
author_facet	Ruben Martín Maria Miana Raquel Jurado-López Ernesto Martínez-Martínez Nieves Gómez-Hurtado Carmen Delgado Maria Visitación Bartolomé José Alberto San Román Claudia Cordova Vicente Lahera Maria Luisa Nieto Victoria Cachofeiro
author_sort	Ruben Martín
title	DIOL triterpenes block profibrotic effects of angiotensin II and protect from cardiac hypertrophy.
title_short	DIOL triterpenes block profibrotic effects of angiotensin II and protect from cardiac hypertrophy.
title_full	DIOL triterpenes block profibrotic effects of angiotensin II and protect from cardiac hypertrophy.
title_fullStr	DIOL triterpenes block profibrotic effects of angiotensin II and protect from cardiac hypertrophy.
title_full_unstemmed	DIOL triterpenes block profibrotic effects of angiotensin II and protect from cardiac hypertrophy.
title_sort	diol triterpenes block profibrotic effects of angiotensin ii and protect from cardiac hypertrophy.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/31318f08ff3e4b7fa18ce0a62795e37e
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DIOL triterpenes block profibrotic effects of angiotensin II and protect from cardiac hypertrophy.

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