Impact of alcohol consumption on the outcome of ischemic stroke and thrombolysis: role of the hepatic clearance of tissue-type plasminogen activator

Eloïse Lemarchand; Maxime Gauberti; Sara Martinez de Lizarrondo; Hélène Villain; Yohann Repessé; Axel Montagne; Denis Vivien; Carine Ali; Marina Rubio

doi:10.1161/STROKEAHA.114.007143

Impact of alcohol consumption on the outcome of ischemic stroke and thrombolysis: role of the hepatic clearance of tissue-type plasminogen activator

Eloïse Lemarchand, Maxime Gauberti, Sara Martinez de Lizarrondo, Hélène Villain, Yohann Repessé, Axel Montagne, Denis Vivien, Carine Ali, Marina Rubio

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

BACKGROUND AND PURPOSE: Tissue-type plasminogen activator (tPA) is the only acute treatment for ischemic stroke. Unfortunately, the benefit of tPA-driven thrombolysis is not systematic, and understanding the reasons for this is mandatory. The balance between beneficial and detrimental effects of tPA might explain the limited overall efficiency of thrombolysis. Here, we investigated whether this balance could be influenced by excessive alcohol intake.

METHODS: We used a murine model of thromboembolic stroke, coupled to an array of biochemical assays, near-infrared or magnetic resonance imaging scans, 2-photon microscopy, hydrodynamic transfections, and immunohistological techniques.

RESULTS: We found that 6 weeks of alcohol consumption (10% in drinking water) worsens ischemic lesions and cancels the beneficial effects of tPA-induced thrombolysis. We accumulate in vivo and in vitro evidence showing that this aggravation is correlated with a decrease in lipoprotein receptor-related protein 1-mediated hepatic clearance of tPA in alcohol-exposed mice.

CONCLUSIONS: An efficient liver-driven clearance of tPA might influence the safety of thrombolysis after stroke.

Original language	English
Pages (from-to)	1641-50
Number of pages	10
Journal	Stroke
Volume	46
Issue number	6
DOIs	https://doi.org/10.1161/STROKEAHA.114.007143
Publication status	Published - Jun 2015

Keywords / Materials (for Non-textual outputs)

Alcohol Drinking/adverse effects
Animals
Brain Ischemia/drug therapy
Disease Models, Animal
Liver/metabolism
Low Density Lipoprotein Receptor-Related Protein-1/metabolism
Mice
Stroke/drug therapy
Thrombolytic Therapy
Tissue Plasminogen Activator/pharmacokinetics

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10.1161/STROKEAHA.114.007143

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@article{a9fb6dd0ae2c4637aac230eac9db9da9,

title = "Impact of alcohol consumption on the outcome of ischemic stroke and thrombolysis: role of the hepatic clearance of tissue-type plasminogen activator",

abstract = "BACKGROUND AND PURPOSE: Tissue-type plasminogen activator (tPA) is the only acute treatment for ischemic stroke. Unfortunately, the benefit of tPA-driven thrombolysis is not systematic, and understanding the reasons for this is mandatory. The balance between beneficial and detrimental effects of tPA might explain the limited overall efficiency of thrombolysis. Here, we investigated whether this balance could be influenced by excessive alcohol intake.METHODS: We used a murine model of thromboembolic stroke, coupled to an array of biochemical assays, near-infrared or magnetic resonance imaging scans, 2-photon microscopy, hydrodynamic transfections, and immunohistological techniques.RESULTS: We found that 6 weeks of alcohol consumption (10% in drinking water) worsens ischemic lesions and cancels the beneficial effects of tPA-induced thrombolysis. We accumulate in vivo and in vitro evidence showing that this aggravation is correlated with a decrease in lipoprotein receptor-related protein 1-mediated hepatic clearance of tPA in alcohol-exposed mice.CONCLUSIONS: An efficient liver-driven clearance of tPA might influence the safety of thrombolysis after stroke.",

keywords = "Alcohol Drinking/adverse effects, Animals, Brain Ischemia/drug therapy, Disease Models, Animal, Liver/metabolism, Low Density Lipoprotein Receptor-Related Protein-1/metabolism, Mice, Stroke/drug therapy, Thrombolytic Therapy, Tissue Plasminogen Activator/pharmacokinetics",

author = "Elo{\"i}se Lemarchand and Maxime Gauberti and {Martinez de Lizarrondo}, Sara and H{\'e}l{\`e}ne Villain and Yohann Repess{\'e} and Axel Montagne and Denis Vivien and Carine Ali and Marina Rubio",

note = "{\textcopyright} 2015 American Heart Association, Inc.",

year = "2015",

month = jun,

doi = "10.1161/STROKEAHA.114.007143",

language = "English",

volume = "46",

pages = "1641--50",

journal = "Stroke",

issn = "0039-2499",

publisher = "Lippincott Williams & Wilkins",

number = "6",

}

TY - JOUR

T1 - Impact of alcohol consumption on the outcome of ischemic stroke and thrombolysis

T2 - role of the hepatic clearance of tissue-type plasminogen activator

AU - Lemarchand, Eloïse

AU - Gauberti, Maxime

AU - Martinez de Lizarrondo, Sara

AU - Villain, Hélène

AU - Repessé, Yohann

AU - Montagne, Axel

AU - Vivien, Denis

AU - Ali, Carine

AU - Rubio, Marina

PY - 2015/6

Y1 - 2015/6

N2 - BACKGROUND AND PURPOSE: Tissue-type plasminogen activator (tPA) is the only acute treatment for ischemic stroke. Unfortunately, the benefit of tPA-driven thrombolysis is not systematic, and understanding the reasons for this is mandatory. The balance between beneficial and detrimental effects of tPA might explain the limited overall efficiency of thrombolysis. Here, we investigated whether this balance could be influenced by excessive alcohol intake.METHODS: We used a murine model of thromboembolic stroke, coupled to an array of biochemical assays, near-infrared or magnetic resonance imaging scans, 2-photon microscopy, hydrodynamic transfections, and immunohistological techniques.RESULTS: We found that 6 weeks of alcohol consumption (10% in drinking water) worsens ischemic lesions and cancels the beneficial effects of tPA-induced thrombolysis. We accumulate in vivo and in vitro evidence showing that this aggravation is correlated with a decrease in lipoprotein receptor-related protein 1-mediated hepatic clearance of tPA in alcohol-exposed mice.CONCLUSIONS: An efficient liver-driven clearance of tPA might influence the safety of thrombolysis after stroke.

AB - BACKGROUND AND PURPOSE: Tissue-type plasminogen activator (tPA) is the only acute treatment for ischemic stroke. Unfortunately, the benefit of tPA-driven thrombolysis is not systematic, and understanding the reasons for this is mandatory. The balance between beneficial and detrimental effects of tPA might explain the limited overall efficiency of thrombolysis. Here, we investigated whether this balance could be influenced by excessive alcohol intake.METHODS: We used a murine model of thromboembolic stroke, coupled to an array of biochemical assays, near-infrared or magnetic resonance imaging scans, 2-photon microscopy, hydrodynamic transfections, and immunohistological techniques.RESULTS: We found that 6 weeks of alcohol consumption (10% in drinking water) worsens ischemic lesions and cancels the beneficial effects of tPA-induced thrombolysis. We accumulate in vivo and in vitro evidence showing that this aggravation is correlated with a decrease in lipoprotein receptor-related protein 1-mediated hepatic clearance of tPA in alcohol-exposed mice.CONCLUSIONS: An efficient liver-driven clearance of tPA might influence the safety of thrombolysis after stroke.

KW - Alcohol Drinking/adverse effects

KW - Animals

KW - Brain Ischemia/drug therapy

KW - Disease Models, Animal

KW - Liver/metabolism

KW - Low Density Lipoprotein Receptor-Related Protein-1/metabolism

KW - Mice

KW - Stroke/drug therapy

KW - Thrombolytic Therapy

KW - Tissue Plasminogen Activator/pharmacokinetics

U2 - 10.1161/STROKEAHA.114.007143

DO - 10.1161/STROKEAHA.114.007143

M3 - Article

C2 - 25922513

SN - 0039-2499

VL - 46

SP - 1641

EP - 1650

JO - Stroke

JF - Stroke

IS - 6

ER -

Impact of alcohol consumption on the outcome of ischemic stroke and thrombolysis: role of the hepatic clearance of tissue-type plasminogen activator

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Keywords / Materials (for Non-textual outputs)

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