Inhibition of GTPase Rac1 expression by vitamin D mitigates pressure overload-induced cardiac hypertrophy

Background: 1, 25-dihydroxy Vitamin D3 (VitD) attenuates left ventricular hypertrophy (LVH), but the mechanisms remain to be portrayed in-depth. The small GTPase Rac1 plays a pivotal role in cardiovascular pathology, especially LVH. Here, we tested whether VitD exerts its anti-LVH effects by counter...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Ali Moradi, Abdulbaset Maroofi, Mahdie Hemati, Tahmine Hashemzade, Nasrin Alborzi, Fatemeh Safari
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Hypertension Left ventricular hypertrophy GTPase Rac1 Vitamin D Diseases of the circulatory (Cardiovascular) system RC666-701
Acceso en línea:	https://doaj.org/article/ee59d877f64a4c8fbe7f0976c8b03b6a
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:ee59d877f64a4c8fbe7f0976c8b03b6a
record_format	dspace
spelling	oai:doaj.org-article:ee59d877f64a4c8fbe7f0976c8b03b6a2021-12-02T05:02:11ZInhibition of GTPase Rac1 expression by vitamin D mitigates pressure overload-induced cardiac hypertrophy2352-906710.1016/j.ijcha.2021.100922https://doaj.org/article/ee59d877f64a4c8fbe7f0976c8b03b6a2021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2352906721002104https://doaj.org/toc/2352-9067Background: 1, 25-dihydroxy Vitamin D3 (VitD) attenuates left ventricular hypertrophy (LVH), but the mechanisms remain to be portrayed in-depth. The small GTPase Rac1 plays a pivotal role in cardiovascular pathology, especially LVH. Here, we tested whether VitD exerts its anti-LVH effects by counteracting the small GTPase Rac1 expression. Methods: In Wistar rats, pressure overload-induced LVH was created by abdominal aortic banding. The animals were intraperitoneally administered VitD (0.1 µg/kg/d). Blood pressure was measured via carotid artery cannulation. Real-time RT-PCR and Western blotting were performed to assess the mRNA and protein expression, respectively. Myocardium was stained for determination of cardiomyocytes area and fibrosis. Lipid peroxidation levels and the activities of antioxidant enzymes were measured in left ventricular tissue. Results: VitD significantly reduced hypertrophy markers (blood pressure, heart-to-body weight ratio, cardiomyocytes area, fibrosis as well as atrial and brain natriuretic peptides mRNA levels) compared to untreated groups (P < 0.05). VitD also improved the activity of antioxidant enzymes and reduced lipid peroxidation levels in the myocardium (P < 0.05). LVH hearts of untreated animals displayed a significant increase in Rac1 expression compared with the control group (P < 0.05). In contrast, cardiac Rac1, at either mRNAs or protein levels, was markedly lower in LVH animals receiving VitD compared with their untreated counterparts (P < 0.05). Conclusion: Our findings attest that VitD mitigates hallmarks of LVH imparted by pressure overload. Notably, VitD appears to perform its anti-LVH function partly through small GTPase Rac1 suppression. This, in turn, provides a robust incentive to consider VitD before LVH culminates in HF devastating disease.Ali MoradiAbdulbaset MaroofiMahdie HematiTahmine HashemzadeNasrin AlborziFatemeh SafariElsevierarticleHypertensionLeft ventricular hypertrophyGTPase Rac1Vitamin DDiseases of the circulatory (Cardiovascular) systemRC666-701ENInternational Journal of Cardiology: Heart & Vasculature, Vol 37, Iss , Pp 100922- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Hypertension Left ventricular hypertrophy GTPase Rac1 Vitamin D Diseases of the circulatory (Cardiovascular) system RC666-701
spellingShingle	Hypertension Left ventricular hypertrophy GTPase Rac1 Vitamin D Diseases of the circulatory (Cardiovascular) system RC666-701 Ali Moradi Abdulbaset Maroofi Mahdie Hemati Tahmine Hashemzade Nasrin Alborzi Fatemeh Safari Inhibition of GTPase Rac1 expression by vitamin D mitigates pressure overload-induced cardiac hypertrophy
description	Background: 1, 25-dihydroxy Vitamin D3 (VitD) attenuates left ventricular hypertrophy (LVH), but the mechanisms remain to be portrayed in-depth. The small GTPase Rac1 plays a pivotal role in cardiovascular pathology, especially LVH. Here, we tested whether VitD exerts its anti-LVH effects by counteracting the small GTPase Rac1 expression. Methods: In Wistar rats, pressure overload-induced LVH was created by abdominal aortic banding. The animals were intraperitoneally administered VitD (0.1 µg/kg/d). Blood pressure was measured via carotid artery cannulation. Real-time RT-PCR and Western blotting were performed to assess the mRNA and protein expression, respectively. Myocardium was stained for determination of cardiomyocytes area and fibrosis. Lipid peroxidation levels and the activities of antioxidant enzymes were measured in left ventricular tissue. Results: VitD significantly reduced hypertrophy markers (blood pressure, heart-to-body weight ratio, cardiomyocytes area, fibrosis as well as atrial and brain natriuretic peptides mRNA levels) compared to untreated groups (P < 0.05). VitD also improved the activity of antioxidant enzymes and reduced lipid peroxidation levels in the myocardium (P < 0.05). LVH hearts of untreated animals displayed a significant increase in Rac1 expression compared with the control group (P < 0.05). In contrast, cardiac Rac1, at either mRNAs or protein levels, was markedly lower in LVH animals receiving VitD compared with their untreated counterparts (P < 0.05). Conclusion: Our findings attest that VitD mitigates hallmarks of LVH imparted by pressure overload. Notably, VitD appears to perform its anti-LVH function partly through small GTPase Rac1 suppression. This, in turn, provides a robust incentive to consider VitD before LVH culminates in HF devastating disease.
format	article
author	Ali Moradi Abdulbaset Maroofi Mahdie Hemati Tahmine Hashemzade Nasrin Alborzi Fatemeh Safari
author_facet	Ali Moradi Abdulbaset Maroofi Mahdie Hemati Tahmine Hashemzade Nasrin Alborzi Fatemeh Safari
author_sort	Ali Moradi
title	Inhibition of GTPase Rac1 expression by vitamin D mitigates pressure overload-induced cardiac hypertrophy
title_short	Inhibition of GTPase Rac1 expression by vitamin D mitigates pressure overload-induced cardiac hypertrophy
title_full	Inhibition of GTPase Rac1 expression by vitamin D mitigates pressure overload-induced cardiac hypertrophy
title_fullStr	Inhibition of GTPase Rac1 expression by vitamin D mitigates pressure overload-induced cardiac hypertrophy
title_full_unstemmed	Inhibition of GTPase Rac1 expression by vitamin D mitigates pressure overload-induced cardiac hypertrophy
title_sort	inhibition of gtpase rac1 expression by vitamin d mitigates pressure overload-induced cardiac hypertrophy
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/ee59d877f64a4c8fbe7f0976c8b03b6a
work_keys_str_mv	AT alimoradi inhibitionofgtpaserac1expressionbyvitamindmitigatespressureoverloadinducedcardiachypertrophy AT abdulbasetmaroofi inhibitionofgtpaserac1expressionbyvitamindmitigatespressureoverloadinducedcardiachypertrophy AT mahdiehemati inhibitionofgtpaserac1expressionbyvitamindmitigatespressureoverloadinducedcardiachypertrophy AT tahminehashemzade inhibitionofgtpaserac1expressionbyvitamindmitigatespressureoverloadinducedcardiachypertrophy AT nasrinalborzi inhibitionofgtpaserac1expressionbyvitamindmitigatespressureoverloadinducedcardiachypertrophy AT fatemehsafari inhibitionofgtpaserac1expressionbyvitamindmitigatespressureoverloadinducedcardiachypertrophy
_version_	1718400805207277568

Inhibition of GTPase Rac1 expression by vitamin D mitigates pressure overload-induced cardiac hypertrophy

Ejemplares similares