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31 results on '"Poole, Lauren G."'

9. Fibrinolysis-Mediated Pathways in Acute Liver Injury.

Author

Capece, Gina E., Luyendyk, James P., and Poole, Lauren G.

Subjects
LIVER injuries, PLASMINOGEN activators, ANTIFIBRINOLYTIC agents, TISSUE plasminogen activator, BACTERIAL diseases
Abstract

Acute liver injury (ALI), that is, the development of reduced liver function in patients without preexisting liver disease, can result from a wide range of causes, such as viral or bacterial infection, autoimmune disease, or adverse reaction to prescription and over-the-counter medications. ALI patients present with a complex coagulopathy, characterized by both hypercoagulable and hypocoagulable features. Similarly, ALI patients display a profound dysregulation of the fibrinolytic system with the vast majority of patients presenting with a hypofibrinolytic phenotype. Decades of research in experimental acute liver injury in mice suggest that fibrinolytic proteins, including plasmin(ogen), plasminogen activators, fibrinolysis inhibitors, and fibrin(ogen), can contribute to initial hepatotoxicity and/or stimulate liver repair. This review summarizes major experimental findings regarding the role of fibrinolytic factors in ALI from the last approximately 30 years and identifies unanswered questions, as well as highlighting areas for future research. [ABSTRACT FROM AUTHOR]

Published
2024
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11. Coagulation factor XIII is a critical driver of liver regeneration after partial hepatectomy.

Author

Wei, Zimu, primary, Groeneveld, Dafna J., additional, Adelmeijer, Jelle, additional, Poole, Lauren G., additional, Cline, Holly, additional, Kern, Anna E., additional, Langer, Brigitte, additional, Brunnthaler, Laura, additional, Assinger, Alice, additional, Starlinger, Patrick, additional, Lisman, Ton, additional, and Luyendyk, James P., additional

Published
2023
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16. Altered fibrinogen γ-chain cross-linking in mutant fibrinogen-γΔ5mice drives acute liver injury

Author

Poole, Lauren G., Schmitt, Lauren R., Schulte, Anthony, Groeneveld, Dafna J., Cline, Holly M., Sang, Yaqiu, Hur, Woosuk S., Wolberg, Alisa S., Flick, Matthew J., Hansen, Kirk C., and Luyendyk, James P.

Abstract

Hepatic deposition of cross-linked fibrin(ogen) occurs alongside platelet accumulation as a hallmark of acetaminophen (APAP)-induced liver injury.

Published
2023
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20. Proceedings of the 16th Annual UT-KBRIN Bioinformatics Summit 2016: proceedings: Burns, TN, USA. April 21-23, 2017

Author

Dent, L. Leon, Mandape, Sammed N., Pratap, Siddharth, Dong, Jianan, Davis, Jamaine, Gaddy, Jennifer A., Amoah, Kofi, Damo, Steve, Marshall, Dana R., Jones, Jacob, Brandt, Toni, Diaz, Gilberto, Wang, Qingguo, Gary, Todd, Yenamandra, Ashwini, Ghattas, Marina Z., Elrakaiby, Marwa, Aziz, Ramy K., Zedan, Hamdallah H., Elmassry, Moamen, ElRakaiby, Marwa, Aziz, Ramy K., Lotfy, Mariam, Elmassry, Moamen, Marcel, Jarrad, Khattab, Rania A., Abdelfattah, Maha M., Gilbert, Jack A., Aziz, Ramy K., Dini, Pouya, Loux, Shavahn C., Scoggin, Kirsten E., Esteller-Vico, Alejandro, Squires, Edward L., Troedsson, Mats H. T., Daels, Peter, Ball, Barry A., De Silva, Kalpani, Bailey, Ernest, Stephens, Joel C., Kalbfleisch, Theodore S., Dolin, Christine E., Poole, Lauren G., Wilkey, Daniel W., Rouchka, Eric C., Arteel, Gavin E., Barati, Michelle T., Merchant, Michael L., Higashi, Richard M., Fan, Teresa W-M, Moseley, Hunter, and Lane, Andrew N

Published
2017
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23. Direct Amplification of Tissue Factor:Factor VIIa Procoagulant Activity by Bile Acids Drives Intrahepatic Coagulation

Author

Baker, Kevin S., primary, Kopec, Anna K., additional, Pant, Asmita, additional, Poole, Lauren G., additional, Cline-Fedewa, Holly, additional, Ivkovich, Dora, additional, Olyaee, Mojtaba, additional, Woolbright, Benjamin L., additional, Miszta, Adam, additional, Jaeschke, Hartmut, additional, Wolberg, Alisa S., additional, and Luyendyk, James P., additional

Published
2019
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24. Transitional Remodeling of the Hepatic Extracellular Matrix in Alcohol-Induced Liver Injury

Author

Poole, Lauren G. and Arteel, Gavin E.

Subjects
Article Subject
Abstract

Alcohol consumption is a common custom worldwide, and the toxic effects of alcohol on several target organs are well understood. The liver is the primary site of alcohol metabolism and is therefore the major target of alcohol toxicity. Alcoholic liver disease is a spectrum of disease states, ranging from simple steatosis (fat accumulation), to inflammation, and eventually to fibrosis and cirrhosis if untreated. The fibrotic stage of ALD is primarily characterized by robust accumulation of extracellular matrix (ECM) proteins (collagens) which ultimately impairs the function of the organ. The role of the ECM in early stages of ALD is poorly understood, but recent research has demonstrated that a number of changes in the hepatic ECM in prefibrotic ALD not only are present, but may also contribute to disease progression. The purpose of this review is to summarize the established and proposed changes to the hepatic extracellular matrix (ECM) that may contribute to earlier stages of ALD development and to discuss potential mechanisms by which these changes may mediate the progression of the disease.

Published
2016
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27. Organ-Organ Crosstalk and Alcoholic Liver Disease.

Author

Poole, Lauren G., Dolin, Christine E., and Arteel, Gavin E.

Subjects
*ALCOHOLIC liver diseases, *TREATMENT effectiveness, *BIOLOGICAL crosstalk, *THERAPEUTICS
Abstract

Alcohol consumption is a common custom worldwide, and the toxic effects of alcohol on several target organs are well-understood. Given the poor prognosis of treating clinically-relevant alcoholic liver disease (ALD) (i.e., alcoholic hepatitis (AH) and cirrhosis), additional research is required to develop more effective therapies. While the stages of ALD have been well-characterized, targeted therapies to prevent or reverse this process in humans are still needed. Better understanding of risk factors and mechanisms underlying disease progression can lead to the development of rational therapies to prevent or reverse ALD in the clinic. A potential area of targeted therapy for ALD may be organ-organ communication in the early stages of the disease. In contrast to AH and end-stage liver diseases, the involvement of multiple organs in the development of ALD is less understood. The impact of these changes on pathology to the liver and other organs may not only influence disease progression during the development of the disease, but also outcomes of end stages diseases. The purpose of this review is to summarize the established and proposed communication between the liver and other organ systems that may contribute to the development and progression of liver disease, as well as to other organs. Potential mechanisms of this organ-organ communication are also discussed. [ABSTRACT FROM AUTHOR]

Published
2017
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29. Hypofibrinogenemia with preserved hemostasis and protection from thrombosis in mice with a Fgatruncation mutation

Author

Hur, Woosuk S, Paul, David S, Bouck, Emma G, Negrón, Oscar A, Mwiza, Jean-Marie, Poole, Lauren G, Cline-Fedewa, Holly M, Clark, Emily G, Juang, Lih Jiin, Leung, Jerry, Kastrup, Christian, Ugarova, Tatiana P, Wolberg, Alisa S, Luyendyk, James P, Bergmeier, Wolfgang, and Flick, Matthew J

Abstract

Genetic variants within the fibrinogen Aα-chain encoding the αC-region commonly result in hypodysfibrinogenemia in patients. However, the (patho)physiological consequences and underlying mechanisms of such mutations remain undefined. Here, we generated Fga270mice carrying a premature termination codon within the Fgagene at residue 271. The Fga270mutation was compatible with Mendelian inheritance for offspring of heterozygous crosses. Adult Fga270/270mice were hypofibrinogenemic with~10% plasma fibrinogen levels relative to FgaWT/WTmice, linked to 90% reduction in hepatic FgamRNA due to nonsense-mediated decay of the mutant mRNA. Fga270/270mice had preservedhemostatic potential in vitroand in vivoin models of tail bleeding and laser-induced saphenous vein injury, while Fga-/-mice had continuous bleeding. Platelets from FgaWT/WTandFga270/270mice displayed comparable initial aggregation following ADP stimulation, but Fga270/270platelets quickly disaggregated. Despite ~10% plasma fibrinogen, the fibrinogen level in Fga270/270platelets was ~30% of FgaWT/WTplatelets with a compensatory increase in fibronectin. Notably, Fga270/270mice showed complete protection from thrombosis in the inferior vena cavastasis model. In a modelof Staphylococcus aureusperitonitis, Fga270/270mice supported local, fibrinogen-mediated bacterial clearance and host survival comparable to FgaWT/WT, unlike Fga-/-mice. Decreasing the normal fibrinogen levels to ~10% with siRNA in mice also provided significant protection from venous thrombosis without compromising hemostatic potential and antimicrobial function. These findings both reveal novel molecular mechanismsunderpinning fibrinogen αC-region truncation mutations and highlight the concept that selective fibrinogen reduction may be efficacious for limiting thrombosis while preserving hemostatic and immune protective functions.

Published
2021
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30. Novel insight into the liver-lung axis in alcohol-enhanced acute lung injury.

Author

Poole, Lauren G.

Subjects
Pharmacology, Toxicology
Abstract

Background. Individuals who chronically abuse alcohol are almost 4 times more likely to develop Acute Respiratory Distress Syndrome (ARDS), the most severe form of Acute Lung Injury (ALI), but the mechanisms by which alcohol abuse sensitizes the lung to injury are poorly understood. However, the lung appears to share many parallel mechanisms of injury with the liver- a primary target of alcohol abuse. The overarching goal of this dissertation was therefore to expand on established mechanisms of alcohol-induced liver injury to ask innovative questions about mechanisms of alcohol-enhanced acute lung injury, as well as to develop new tools that may be used to gain novel insight into the liver-lung axis of alcoholinduced injury. Methods. Male mice were exposed to ethanol containing liquid diet either chronically (6 weeks) or in a chronic + binge pattern. Some mice were administered lipopolysaccharide (LPS) to induce acute lung injury. Lung injury and inflammation were assessed. To develop an animal model by which liver-lung interactions could be investigated, tamoxifen-loaded polymer nanoparticles were administered intrasplenically to a tamoxifen-inducible, Cre-mediated, dual-fluorescent reporter construct. Results. Chapter III of this dissertation describes a mechanism by which plasminogen activator inhibitor-1 (PAI-1) is involved in alcoholenhanced acute lung injury. Specifically, it was proposed that PAI-1-mediated fibrin accumulation promotes the aggregation of platelets, thereby propagating lung injury and inflammation. Chapter IV of this dissertation characterizes a recently-developed animal model of chronic + binge alcohol exposure, finding that animals exposed to chronic + binge alcohol exposure exhibit pulmonary inflammation and airway hyperresponsiveness. Finally, Chapter V of this dissertation develops an animal model to investigate liver-lung interactions during chronic alcohol exposure. It was found that tamoxifen-loaded polymer nanoparticles, when administered intrasplenically, selectively alter the genetics of hepatic cells, while avoiding other tissues, including the lung. Discussion. The work presented in this dissertation has, in conclusion, uncovered novel mechanisms by which alcohol sensitizes the lung to a second injury, shown that ethanol alone is sufficient to cause lung inflammation, and developed a novel animal method to examine liver-lung interactions during alcohol exposure.

Published
2017

31. Chronic ethanol exposure sensitizes the lung in a mouse model of endotoxemia-induced acute lung injury : potential role of plasminogen activator inhibitor-1.

Author

Poole, Lauren G.

Subjects
Pharmacy and Pharmaceutical Sciences
Abstract

The goal of this project is to characterize a new mouse model of alcohol-enhanced acute lung injury (ALI) and to determine the role of plasminogen activator inhibitor-1 (PAI-1) in this model. Male mice (WT and PAI-1-/-) were exposed to ethanol-containing Lieber-DeCarli diet or pair-fed control diet for 6 weeks; some animals were administered intraperitoneal lipopolysaccharide (LPS) prior to sacrifice. Chronic alcohol feeding enhanced induction of the chemokines MIP-2 and KC (murine IL-8 homologues) after LPS injection in wild type animals. This enhanced chemokine expression did not correlate with enhanced pulmonary neutrophil infiltration, however animals exposed to chronic ethanol showed sustained alveolar septal thickening and enhanced 4-HNE staining, indicative of inflammatory damage. Septal thickening was completely attenuated in PAI-1-/- animals. This work has developed a new mouse model which can be used to elucidate the mechanisms of alcohol-enhanced ALI. A potential role of PAI-1 in alcohol-enhanced ALI has also been identified.

Published
2015

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