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Enzymatic changes in myosin regulatory proteins may explain vasoplegia in terminally ill patients with sepsis
The current study was conducted with the hypothesis that failure of maintenance of the vascular tone may be central to failure of the peripheral circulation and spiralling down of blood pressure in sepsis. Namely, we examined the balance between expression of myosin light chain (MLC) phosphatase and...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Portland Press Ltd.
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4776626/ https://www.ncbi.nlm.nih.gov/pubmed/26772992 http://dx.doi.org/10.1042/BSR20150207 |
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author | Zheng, Wentao Kou, Yong Gao, Feng-lan Ouyang, Xiu-he |
author_facet | Zheng, Wentao Kou, Yong Gao, Feng-lan Ouyang, Xiu-he |
author_sort | Zheng, Wentao |
collection | PubMed |
description | The current study was conducted with the hypothesis that failure of maintenance of the vascular tone may be central to failure of the peripheral circulation and spiralling down of blood pressure in sepsis. Namely, we examined the balance between expression of myosin light chain (MLC) phosphatase and kinase, enzymes that regulate MLCs dephosphorylation and phosphorylation with a direct effect on pharmacomechanical coupling for smooth muscle relaxation and contraction respectively. Mechanical recordings and enzyme immunoassays of vascular smooth muscle lysates were used as the major methods to examine arterial biopsy samples from terminally ill sepsis patients. The results of the present study provide evidence that genomic alteration of expression of key regulatory proteins in vascular smooth muscles may be responsible for the relentless downhill course in sepsis. Down-regulation of myosin light chain kinase (MLCK) and up-regulation of MLCK may explain the loss of tone and failure to mount contractile response in vivo during circulation. The mechanical studies demonstrated the inability of the arteries to develop tone when stimulated by phenylephrine in vitro. The results of our study provide indirect hint that control of inflammation is a major therapeutic approach in sepsis, and may facilitate to ameliorate the progressive cardiovascular collapse. |
format | Online Article Text |
id | pubmed-4776626 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Portland Press Ltd. |
record_format | MEDLINE/PubMed |
spelling | pubmed-47766262016-04-01 Enzymatic changes in myosin regulatory proteins may explain vasoplegia in terminally ill patients with sepsis Zheng, Wentao Kou, Yong Gao, Feng-lan Ouyang, Xiu-he Biosci Rep Original Papers The current study was conducted with the hypothesis that failure of maintenance of the vascular tone may be central to failure of the peripheral circulation and spiralling down of blood pressure in sepsis. Namely, we examined the balance between expression of myosin light chain (MLC) phosphatase and kinase, enzymes that regulate MLCs dephosphorylation and phosphorylation with a direct effect on pharmacomechanical coupling for smooth muscle relaxation and contraction respectively. Mechanical recordings and enzyme immunoassays of vascular smooth muscle lysates were used as the major methods to examine arterial biopsy samples from terminally ill sepsis patients. The results of the present study provide evidence that genomic alteration of expression of key regulatory proteins in vascular smooth muscles may be responsible for the relentless downhill course in sepsis. Down-regulation of myosin light chain kinase (MLCK) and up-regulation of MLCK may explain the loss of tone and failure to mount contractile response in vivo during circulation. The mechanical studies demonstrated the inability of the arteries to develop tone when stimulated by phenylephrine in vitro. The results of our study provide indirect hint that control of inflammation is a major therapeutic approach in sepsis, and may facilitate to ameliorate the progressive cardiovascular collapse. Portland Press Ltd. 2016-03-03 /pmc/articles/PMC4776626/ /pubmed/26772992 http://dx.doi.org/10.1042/BSR20150207 Text en © 2016 Authors http://creativecommons.org/licenses/by/3.0/ This is an open access article published by Portland Press Limited and distributed under the Creative Commons Attribution Licence 3.0 (http://creativecommons.org/licenses/by/3.0/) . |
spellingShingle | Original Papers Zheng, Wentao Kou, Yong Gao, Feng-lan Ouyang, Xiu-he Enzymatic changes in myosin regulatory proteins may explain vasoplegia in terminally ill patients with sepsis |
title | Enzymatic changes in myosin regulatory proteins may explain vasoplegia in terminally ill patients with sepsis |
title_full | Enzymatic changes in myosin regulatory proteins may explain vasoplegia in terminally ill patients with sepsis |
title_fullStr | Enzymatic changes in myosin regulatory proteins may explain vasoplegia in terminally ill patients with sepsis |
title_full_unstemmed | Enzymatic changes in myosin regulatory proteins may explain vasoplegia in terminally ill patients with sepsis |
title_short | Enzymatic changes in myosin regulatory proteins may explain vasoplegia in terminally ill patients with sepsis |
title_sort | enzymatic changes in myosin regulatory proteins may explain vasoplegia in terminally ill patients with sepsis |
topic | Original Papers |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4776626/ https://www.ncbi.nlm.nih.gov/pubmed/26772992 http://dx.doi.org/10.1042/BSR20150207 |
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