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Role of ROCK upregulation in endothelial and smooth muscle vascular functions in diabetic rat aorta

BACKGROUND: The RhoA/ROCK signaling pathway mediates vascular smooth muscle contraction while endogenous NO induces vasodilation through its inhibition. Since myosin light chain phosphatase (MLCP) and eNOS are targeted by RhoA/ROCK upregulation then turn to lead abnormalities in vasculature, we aime...

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Autores principales: Cicek, Figen Amber, Kandilci, Hilmi B, Turan, Belma
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3620917/
https://www.ncbi.nlm.nih.gov/pubmed/23530857
http://dx.doi.org/10.1186/1475-2840-12-51
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author Cicek, Figen Amber
Kandilci, Hilmi B
Turan, Belma
author_facet Cicek, Figen Amber
Kandilci, Hilmi B
Turan, Belma
author_sort Cicek, Figen Amber
collection PubMed
description BACKGROUND: The RhoA/ROCK signaling pathway mediates vascular smooth muscle contraction while endogenous NO induces vasodilation through its inhibition. Since myosin light chain phosphatase (MLCP) and eNOS are targeted by RhoA/ROCK upregulation then turn to lead abnormalities in vasculature, we aimed to examine whether less endothelial NO-production and inhibited eNOS together with an upregulation of RhoA/ROCK signaling pathway in thoracic aorta can play an important role in vascular dysfunction under hyperglycemia. METHODS: We used streptozotocin-injected rats, as a model of type 1 diabetes, and their lean controls to investigate the role of ROCK upregulation in the function of toracic aorta by using electrophysiological and biochemical techniques. RESULTS: The protein level of ROCK isoform ROCK2 was found to be 2.5-fold higher in endothelium-intact aortic rings of the diabetic rats compared to those of the controls while its level in endothelium-denuded rings was similar among these two groups. Phosphorylation level of eNOS in endothelium-intact rings from the diabetics was 50% less compared to that of the control. ROCK inhibitors, either Y27632 or HA1077, induced concentration-dependent relaxation with a marked left-shift in phenylephrine pre-contracted endothelium-intact rings from either diabetics or high glucose incubated controls while pretreatment of these rings with L-NAME abolished this shift, fully. Moreover, phosphorylation levels of both MLCP and MLC in endothelium-denuded rings were markedly higher in the diabetics than the controls. CONCLUSION: We demonstrated that diabetes-induced vascular dysfunction can arise due to either inbition of eNOS, thereby less endothelial NO-production, either directly or indirectly, in part, due to an upregulation of ROCK2 by hyperglycemia. Additionally, our data demonstrate that high phosphorylation levels of both MLC and MLCP in endothelium-denuded rings can be due to a less endothelial NO-production dependent ROCK upregulation in the smooth muscle cells under hyperglycemia, as well.
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spelling pubmed-36209172013-04-10 Role of ROCK upregulation in endothelial and smooth muscle vascular functions in diabetic rat aorta Cicek, Figen Amber Kandilci, Hilmi B Turan, Belma Cardiovasc Diabetol Original Investigation BACKGROUND: The RhoA/ROCK signaling pathway mediates vascular smooth muscle contraction while endogenous NO induces vasodilation through its inhibition. Since myosin light chain phosphatase (MLCP) and eNOS are targeted by RhoA/ROCK upregulation then turn to lead abnormalities in vasculature, we aimed to examine whether less endothelial NO-production and inhibited eNOS together with an upregulation of RhoA/ROCK signaling pathway in thoracic aorta can play an important role in vascular dysfunction under hyperglycemia. METHODS: We used streptozotocin-injected rats, as a model of type 1 diabetes, and their lean controls to investigate the role of ROCK upregulation in the function of toracic aorta by using electrophysiological and biochemical techniques. RESULTS: The protein level of ROCK isoform ROCK2 was found to be 2.5-fold higher in endothelium-intact aortic rings of the diabetic rats compared to those of the controls while its level in endothelium-denuded rings was similar among these two groups. Phosphorylation level of eNOS in endothelium-intact rings from the diabetics was 50% less compared to that of the control. ROCK inhibitors, either Y27632 or HA1077, induced concentration-dependent relaxation with a marked left-shift in phenylephrine pre-contracted endothelium-intact rings from either diabetics or high glucose incubated controls while pretreatment of these rings with L-NAME abolished this shift, fully. Moreover, phosphorylation levels of both MLCP and MLC in endothelium-denuded rings were markedly higher in the diabetics than the controls. CONCLUSION: We demonstrated that diabetes-induced vascular dysfunction can arise due to either inbition of eNOS, thereby less endothelial NO-production, either directly or indirectly, in part, due to an upregulation of ROCK2 by hyperglycemia. Additionally, our data demonstrate that high phosphorylation levels of both MLC and MLCP in endothelium-denuded rings can be due to a less endothelial NO-production dependent ROCK upregulation in the smooth muscle cells under hyperglycemia, as well. BioMed Central 2013-03-27 /pmc/articles/PMC3620917/ /pubmed/23530857 http://dx.doi.org/10.1186/1475-2840-12-51 Text en Copyright © 2013 Cicek et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Investigation
Cicek, Figen Amber
Kandilci, Hilmi B
Turan, Belma
Role of ROCK upregulation in endothelial and smooth muscle vascular functions in diabetic rat aorta
title Role of ROCK upregulation in endothelial and smooth muscle vascular functions in diabetic rat aorta
title_full Role of ROCK upregulation in endothelial and smooth muscle vascular functions in diabetic rat aorta
title_fullStr Role of ROCK upregulation in endothelial and smooth muscle vascular functions in diabetic rat aorta
title_full_unstemmed Role of ROCK upregulation in endothelial and smooth muscle vascular functions in diabetic rat aorta
title_short Role of ROCK upregulation in endothelial and smooth muscle vascular functions in diabetic rat aorta
title_sort role of rock upregulation in endothelial and smooth muscle vascular functions in diabetic rat aorta
topic Original Investigation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3620917/
https://www.ncbi.nlm.nih.gov/pubmed/23530857
http://dx.doi.org/10.1186/1475-2840-12-51
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