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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...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2013
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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. |
format | Online Article Text |
id | pubmed-3620917 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
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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