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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...

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Autores principales: Zheng, Wentao, Kou, Yong, Gao, Feng-lan, Ouyang, Xiu-he
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2016
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.
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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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