Differential baseline expression and angiotensin II stimulation of leukemia-associated RhoGEF in vascular smooth muscle cells of spontaneously hypertensive rats

Wei-Chiao Chiu,1 Jyh-ming Juang,1,2 Shen-nan Chang,2 Cho-kai Wu,2 Chia-ti Tsai,2 Chuen-den Tseng,2 Yung-zu Tseng,1,2 Ming-Jai Su,3 Fu-tien Chiang1,2,41Graduate Institute of Physiology, National Taiwan University College of Medicine, 2Division of Cardiology, Department of Internal Medicine, National...

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Autores principales:	Chiu WC, Juang JM, Chang SN, Wu CK, Tsai CT, Tseng CD, Tseng YZ, Su MJ, Chiang FT
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2012
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/4c8a06617c994f34bd9ae7a71d925f8f
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spelling	oai:doaj.org-article:4c8a06617c994f34bd9ae7a71d925f8f2021-12-02T05:02:16ZDifferential baseline expression and angiotensin II stimulation of leukemia-associated RhoGEF in vascular smooth muscle cells of spontaneously hypertensive rats1176-91141178-2013https://doaj.org/article/4c8a06617c994f34bd9ae7a71d925f8f2012-12-01T00:00:00Zhttp://www.dovepress.com/differential-baseline-expression-and-angiotensin-ii-stimulation-of-leu-a11669https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Wei-Chiao Chiu,1 Jyh-ming Juang,1,2 Shen-nan Chang,2 Cho-kai Wu,2 Chia-ti Tsai,2 Chuen-den Tseng,2 Yung-zu Tseng,1,2 Ming-Jai Su,3 Fu-tien Chiang1,2,41Graduate Institute of Physiology, National Taiwan University College of Medicine, 2Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, 3Graduate Institute of Pharmacology, National Taiwan University College of Medicine, 4Department of Laboratory Medicine, National Taiwan University College of Medicine, Taipei, Taiwan, Republic of ChinaPurpose: Studies to explore angiotensin II (Ang II) and its downstream signaling pathways via Rho guanine nucleotide exchange factors (RhoGEFs) and RhoA signaling are crucial to understanding the mechanisms of smooth muscle contraction leading to hypertension. This study aimed to investigate the Ang II&ndash;induced expression of RhoGEFs in vascular smooth muscle cells (VSMCs) of spontaneously hypertensive rats (SHRs) and to identify the possible regulator associated with hypertension.Methods: Cultured VSMCs of the aorta from SHRs and Wistar-Kyoto (WKY) rats were treated with or without Ang II or Ang II plus Ang II type 2 receptor antagonists. The expression levels of RhoGEF messenger RNA (mRNA) and protein were determined. To evaluate the changes of aortic ring contractile force in response to Ang II, a nonviral carrier system was adopted to deliver the leukemia-associated RhoGEF (LARG) small interfering RNA via nanoparticles into aortic rings.Results: The baseline mRNA levels of three RhoGEFs in cultured VSMCs of WKY rats did not increase with age, but they were significantly higher in 12-week-old SHRs than in 5-week-old SHRs. Expression levels of LARG mRNA were higher in SHRs than in age-matched WKY rats. The baseline LAGR protein of 12-week-old SHRs was about four times higher than that of WKY rats of the same age. After Ang II stimulation, LAGR protein expression was significantly increased in 12-week-old WKY rats but remained unchanged in 12-week-old SHRs. LARG small interfering RNA was successfully delivered into aortic rings using nanoparticles. LARG knockdown resulted in 12-week-old SHRs showing the greatest reduction in aortic ring contraction.Conclusion: There were differences in age-related RhoGEF expression at baseline and in response to Ang II stimulation between SHRs and WKY rats in this study. Nanotechnology can assist in studying the silencing of LARG in tissue culture. The findings of this study indicate that LARG gene expression may be associated with the genesis of hypertension in SHRs.Keywords: Rho guanine nucleotide exchange factor, leukemia-associated Rho guanine nucleotide exchange factor, Wistar-Kyoto rats, nanoparticle delivery, hypertensionChiu WCJuang JMChang SNWu CKTsai CTTseng CDTseng YZSu MJChiang FTDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2012, Iss default, Pp 5929-5939 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Chiu WC Juang JM Chang SN Wu CK Tsai CT Tseng CD Tseng YZ Su MJ Chiang FT Differential baseline expression and angiotensin II stimulation of leukemia-associated RhoGEF in vascular smooth muscle cells of spontaneously hypertensive rats
description	Wei-Chiao Chiu,1 Jyh-ming Juang,1,2 Shen-nan Chang,2 Cho-kai Wu,2 Chia-ti Tsai,2 Chuen-den Tseng,2 Yung-zu Tseng,1,2 Ming-Jai Su,3 Fu-tien Chiang1,2,41Graduate Institute of Physiology, National Taiwan University College of Medicine, 2Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, 3Graduate Institute of Pharmacology, National Taiwan University College of Medicine, 4Department of Laboratory Medicine, National Taiwan University College of Medicine, Taipei, Taiwan, Republic of ChinaPurpose: Studies to explore angiotensin II (Ang II) and its downstream signaling pathways via Rho guanine nucleotide exchange factors (RhoGEFs) and RhoA signaling are crucial to understanding the mechanisms of smooth muscle contraction leading to hypertension. This study aimed to investigate the Ang II&ndash;induced expression of RhoGEFs in vascular smooth muscle cells (VSMCs) of spontaneously hypertensive rats (SHRs) and to identify the possible regulator associated with hypertension.Methods: Cultured VSMCs of the aorta from SHRs and Wistar-Kyoto (WKY) rats were treated with or without Ang II or Ang II plus Ang II type 2 receptor antagonists. The expression levels of RhoGEF messenger RNA (mRNA) and protein were determined. To evaluate the changes of aortic ring contractile force in response to Ang II, a nonviral carrier system was adopted to deliver the leukemia-associated RhoGEF (LARG) small interfering RNA via nanoparticles into aortic rings.Results: The baseline mRNA levels of three RhoGEFs in cultured VSMCs of WKY rats did not increase with age, but they were significantly higher in 12-week-old SHRs than in 5-week-old SHRs. Expression levels of LARG mRNA were higher in SHRs than in age-matched WKY rats. The baseline LAGR protein of 12-week-old SHRs was about four times higher than that of WKY rats of the same age. After Ang II stimulation, LAGR protein expression was significantly increased in 12-week-old WKY rats but remained unchanged in 12-week-old SHRs. LARG small interfering RNA was successfully delivered into aortic rings using nanoparticles. LARG knockdown resulted in 12-week-old SHRs showing the greatest reduction in aortic ring contraction.Conclusion: There were differences in age-related RhoGEF expression at baseline and in response to Ang II stimulation between SHRs and WKY rats in this study. Nanotechnology can assist in studying the silencing of LARG in tissue culture. The findings of this study indicate that LARG gene expression may be associated with the genesis of hypertension in SHRs.Keywords: Rho guanine nucleotide exchange factor, leukemia-associated Rho guanine nucleotide exchange factor, Wistar-Kyoto rats, nanoparticle delivery, hypertension
format	article
author	Chiu WC Juang JM Chang SN Wu CK Tsai CT Tseng CD Tseng YZ Su MJ Chiang FT
author_facet	Chiu WC Juang JM Chang SN Wu CK Tsai CT Tseng CD Tseng YZ Su MJ Chiang FT
author_sort	Chiu WC
title	Differential baseline expression and angiotensin II stimulation of leukemia-associated RhoGEF in vascular smooth muscle cells of spontaneously hypertensive rats
title_short	Differential baseline expression and angiotensin II stimulation of leukemia-associated RhoGEF in vascular smooth muscle cells of spontaneously hypertensive rats
title_full	Differential baseline expression and angiotensin II stimulation of leukemia-associated RhoGEF in vascular smooth muscle cells of spontaneously hypertensive rats
title_fullStr	Differential baseline expression and angiotensin II stimulation of leukemia-associated RhoGEF in vascular smooth muscle cells of spontaneously hypertensive rats
title_full_unstemmed	Differential baseline expression and angiotensin II stimulation of leukemia-associated RhoGEF in vascular smooth muscle cells of spontaneously hypertensive rats
title_sort	differential baseline expression and angiotensin ii stimulation of leukemia-associated rhogef in vascular smooth muscle cells of spontaneously hypertensive rats
publisher	Dove Medical Press
publishDate	2012
url	https://doaj.org/article/4c8a06617c994f34bd9ae7a71d925f8f
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Differential baseline expression and angiotensin II stimulation of leukemia-associated RhoGEF in vascular smooth muscle cells of spontaneously hypertensive rats

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