Statin treatment before stroke reduces pro-inflammatory cytokine levels after stroke

Nicole Elisabeth Ørsted Schultz; Henrik Hasseldam; Rune Skovgaard Rasmussen; Nina Vindegaard; Oskar McWilliam; Helle Klingenberg Iversen; Flemming Fryd Johansen

doi:10.1080/01616412.2018.1558000

Statin treatment before stroke reduces pro-inflammatory cytokine levels after stroke

Nicole Elisabeth Ørsted Schultz, Henrik Hasseldam, Rune Skovgaard Rasmussen, Nina Vindegaard, Oskar McWilliam, Helle Klingenberg Iversen, Flemming Fryd Johansen^*

^*Corresponding author af dette arbejde

Institut for Neurovidenskab

5 Citationer (Scopus)

Abstract

Objective: In this clinical case-control study, we investigated statin treatment in stroke patients on a range of inflammatory effectors in peripheral blood. We focus on RhoA GTPase and its downstream effectors as a future inflammatory target in stroke treatment. Methods: Data from 10 patients already on statins at stroke onset (Pre-S group) was compared with data from both 29 patients starting statin treatment right after stroke onset (Post-S group) and with 8 healthy controls. In T-cells isolated from stroke patients, we analyzed the activity of the main cytoskeletal regulator RhoA GTPase and its downstream effectors: rho-associated protein kinase (ROCK), myosin phosphatase targeting protein subunit 1 (pMYPT1), myosin light chain kinase (pMLC) and cofilin. In the blood samples, we further determined levels of 12 key plasma cytokines as well as C-reactive protein (CRP) and kallikrein. Results: Compared to healthy controls, the Post-S group achieved significantly higher RhoA and ROCK activities, while the Pre-S did not differ from controls. Levels of pMYPT1, pMLC and cofilin did not differ from controls in the Pre-S and Post-S groups. At day 90 after stroke, interferon γ and IL-18 were significantly increased in the Post-S group compared to the Pre-S group. We found a positive correlation between CRP and NIHSS, whereas kallikrein levels showed no correlation with NIHSS at any of the days. Conclusion: Stroke induces changes in the RhoA-ROCK pathway in T-cells. CRP and NIHSS score correlated positively in the study. Statins may have an anti-inflammatory effect as statin treatment before stroke reduces post-stroke pro-inflammatory levels. RhoA GTPase and its downstream effectors are possibly the key to improve statin treatment in stroke.

Originalsprog	Engelsk
Tidsskrift	Neurological Research
Vol/bind	41
Udgave nummer	4
Sider (fra-til)	289-297
Antal sider	10
ISSN	0161-6412
DOI	https://doi.org/10.1080/01616412.2018.1558000
Status	Udgivet - 3 apr. 2019

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10.1080/01616412.2018.1558000

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title = "Statin treatment before stroke reduces pro-inflammatory cytokine levels after stroke",

abstract = "Objective: In this clinical case-control study, we investigated statin treatment in stroke patients on a range of inflammatory effectors in peripheral blood. We focus on RhoA GTPase and its downstream effectors as a future inflammatory target in stroke treatment. Methods: Data from 10 patients already on statins at stroke onset (Pre-S group) was compared with data from both 29 patients starting statin treatment right after stroke onset (Post-S group) and with 8 healthy controls. In T-cells isolated from stroke patients, we analyzed the activity of the main cytoskeletal regulator RhoA GTPase and its downstream effectors: rho-associated protein kinase (ROCK), myosin phosphatase targeting protein subunit 1 (pMYPT1), myosin light chain kinase (pMLC) and cofilin. In the blood samples, we further determined levels of 12 key plasma cytokines as well as C-reactive protein (CRP) and kallikrein. Results: Compared to healthy controls, the Post-S group achieved significantly higher RhoA and ROCK activities, while the Pre-S did not differ from controls. Levels of pMYPT1, pMLC and cofilin did not differ from controls in the Pre-S and Post-S groups. At day 90 after stroke, interferon γ and IL-18 were significantly increased in the Post-S group compared to the Pre-S group. We found a positive correlation between CRP and NIHSS, whereas kallikrein levels showed no correlation with NIHSS at any of the days. Conclusion: Stroke induces changes in the RhoA-ROCK pathway in T-cells. CRP and NIHSS score correlated positively in the study. Statins may have an anti-inflammatory effect as statin treatment before stroke reduces post-stroke pro-inflammatory levels. RhoA GTPase and its downstream effectors are possibly the key to improve statin treatment in stroke.",

keywords = "Clinical study, cytokines, inflammation, statin, stroke",

author = "Schultz, {Nicole Elisabeth {\O}rsted} and Henrik Hasseldam and Rasmussen, {Rune Skovgaard} and Nina Vindegaard and Oskar McWilliam and Iversen, {Helle Klingenberg} and Johansen, {Flemming Fryd}",

year = "2019",

month = apr,

day = "3",

doi = "10.1080/01616412.2018.1558000",

language = "English",

volume = "41",

pages = "289--297",

journal = "Neurological Research",

issn = "0161-6412",

publisher = "Taylor & Francis",

number = "4",

}

TY - JOUR

T1 - Statin treatment before stroke reduces pro-inflammatory cytokine levels after stroke

AU - Schultz, Nicole Elisabeth Ørsted

AU - Hasseldam, Henrik

AU - Rasmussen, Rune Skovgaard

AU - Vindegaard, Nina

AU - McWilliam, Oskar

AU - Iversen, Helle Klingenberg

AU - Johansen, Flemming Fryd

PY - 2019/4/3

Y1 - 2019/4/3

N2 - Objective: In this clinical case-control study, we investigated statin treatment in stroke patients on a range of inflammatory effectors in peripheral blood. We focus on RhoA GTPase and its downstream effectors as a future inflammatory target in stroke treatment. Methods: Data from 10 patients already on statins at stroke onset (Pre-S group) was compared with data from both 29 patients starting statin treatment right after stroke onset (Post-S group) and with 8 healthy controls. In T-cells isolated from stroke patients, we analyzed the activity of the main cytoskeletal regulator RhoA GTPase and its downstream effectors: rho-associated protein kinase (ROCK), myosin phosphatase targeting protein subunit 1 (pMYPT1), myosin light chain kinase (pMLC) and cofilin. In the blood samples, we further determined levels of 12 key plasma cytokines as well as C-reactive protein (CRP) and kallikrein. Results: Compared to healthy controls, the Post-S group achieved significantly higher RhoA and ROCK activities, while the Pre-S did not differ from controls. Levels of pMYPT1, pMLC and cofilin did not differ from controls in the Pre-S and Post-S groups. At day 90 after stroke, interferon γ and IL-18 were significantly increased in the Post-S group compared to the Pre-S group. We found a positive correlation between CRP and NIHSS, whereas kallikrein levels showed no correlation with NIHSS at any of the days. Conclusion: Stroke induces changes in the RhoA-ROCK pathway in T-cells. CRP and NIHSS score correlated positively in the study. Statins may have an anti-inflammatory effect as statin treatment before stroke reduces post-stroke pro-inflammatory levels. RhoA GTPase and its downstream effectors are possibly the key to improve statin treatment in stroke.

AB - Objective: In this clinical case-control study, we investigated statin treatment in stroke patients on a range of inflammatory effectors in peripheral blood. We focus on RhoA GTPase and its downstream effectors as a future inflammatory target in stroke treatment. Methods: Data from 10 patients already on statins at stroke onset (Pre-S group) was compared with data from both 29 patients starting statin treatment right after stroke onset (Post-S group) and with 8 healthy controls. In T-cells isolated from stroke patients, we analyzed the activity of the main cytoskeletal regulator RhoA GTPase and its downstream effectors: rho-associated protein kinase (ROCK), myosin phosphatase targeting protein subunit 1 (pMYPT1), myosin light chain kinase (pMLC) and cofilin. In the blood samples, we further determined levels of 12 key plasma cytokines as well as C-reactive protein (CRP) and kallikrein. Results: Compared to healthy controls, the Post-S group achieved significantly higher RhoA and ROCK activities, while the Pre-S did not differ from controls. Levels of pMYPT1, pMLC and cofilin did not differ from controls in the Pre-S and Post-S groups. At day 90 after stroke, interferon γ and IL-18 were significantly increased in the Post-S group compared to the Pre-S group. We found a positive correlation between CRP and NIHSS, whereas kallikrein levels showed no correlation with NIHSS at any of the days. Conclusion: Stroke induces changes in the RhoA-ROCK pathway in T-cells. CRP and NIHSS score correlated positively in the study. Statins may have an anti-inflammatory effect as statin treatment before stroke reduces post-stroke pro-inflammatory levels. RhoA GTPase and its downstream effectors are possibly the key to improve statin treatment in stroke.

KW - Clinical study

KW - cytokines

KW - inflammation

KW - statin

KW - stroke

U2 - 10.1080/01616412.2018.1558000

DO - 10.1080/01616412.2018.1558000

M3 - Journal article

C2 - 30574850

AN - SCOPUS:85058981961

SN - 0161-6412

VL - 41

SP - 289

EP - 297

JO - Neurological Research

JF - Neurological Research

IS - 4

ER -

Statin treatment before stroke reduces pro-inflammatory cytokine levels after stroke

Abstract

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