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Andrew Leask - One of the best experts on this subject based on the ideXlab platform.

  • wnt1 βcatenin injury response activates the epicardium and Cardiac fibroblasts to promote Cardiac Repair
    The EMBO Journal, 2012
    Co-Authors: Jinzhu Duan, Costin M Gherghe, Dianxin Liu, Eric Hamlett, Luxman Srikantha, Laurel Rodgers, Jenna N Regan, Mauricio Rojas, Monte S Willis, Andrew Leask
    Abstract:

    Wnts are required for cardiogenesis but the role of specific Wnts in Cardiac Repair remains unknown. In this report, we show that a dynamic Wnt1/βcatenin injury response activates the epicardium and Cardiac fibroblasts to promote Cardiac Repair. Acute ischaemic Cardiac injury upregulates Wnt1 that is initially expressed in the epicardium and subsequently by Cardiac fibroblasts in the region of injury. Following Cardiac injury, the epicardium is activated organ‐wide in a Wnt‐dependent manner, expands, undergoes epithelial–mesenchymal transition (EMT) to generate Cardiac fibroblasts, which localize in the subepicardial space. The injured regions in the heart are Wnt responsive as well and Wnt1 induces Cardiac fibroblasts to proliferate and express pro‐fibrotic genes. Disruption of downstream Wnt signalling in epicardial cells decreases epicardial expansion, EMT and leads to impaired Cardiac function and ventricular dilatation after Cardiac injury. Furthermore, disruption of Wnt/βcatenin signalling in Cardiac fibroblasts impairs wound healing and decreases Cardiac performance as well. These findings reveal that a pro‐fibrotic Wnt1/βcatenin injury response is critically required for preserving Cardiac function after acute ischaemic Cardiac injury.

  • Wnt1/βcatenin injury response activates the epicardium and Cardiac fibroblasts to promote Cardiac Repair
    The EMBO Journal, 2011
    Co-Authors: Jinzhu Duan, Costin M Gherghe, Dianxin Liu, Eric Hamlett, Luxman Srikantha, Laurel Rodgers, Jenna N Regan, Mauricio Rojas, Monte S Willis, Andrew Leask
    Abstract:

    Wnts are required for cardiogenesis but the role of specific Wnts in Cardiac Repair remains unknown. In this report, we show that a dynamic Wnt1/βcatenin injury response activates the epicardium and Cardiac fibroblasts to promote Cardiac Repair. Acute ischaemic Cardiac injury upregulates Wnt1 that is initially expressed in the epicardium and subsequently by Cardiac fibroblasts in the region of injury. Following Cardiac injury, the epicardium is activated organ‐wide in a Wnt‐dependent manner, expands, undergoes epithelial–mesenchymal transition (EMT) to generate Cardiac fibroblasts, which localize in the subepicardial space. The injured regions in the heart are Wnt responsive as well and Wnt1 induces Cardiac fibroblasts to proliferate and express pro‐fibrotic genes. Disruption of downstream Wnt signalling in epicardial cells decreases epicardial expansion, EMT and leads to impaired Cardiac function and ventricular dilatation after Cardiac injury. Furthermore, disruption of Wnt/βcatenin signalling in Cardiac fibroblasts impairs wound healing and decreases Cardiac performance as well. These findings reveal that a pro‐fibrotic Wnt1/βcatenin injury response is critically required for preserving Cardiac function after acute ischaemic Cardiac injury.

Jane Hoover-plow - One of the best experts on this subject based on the ideXlab platform.

  • Abstract 245: Plasminogen Augments Cxcl12/cxcr4-regulated Stem Cell Homing And Contributes To Cardiac Repair After Myocardial Infarction.
    Circulation Research, 2014
    Co-Authors: Yanqing Gong, Yujing Zhao, Yi Fan, Jane Hoover-plow
    Abstract:

    Myocardial infarction (MI) is a leading cause of morbidity and mortality worldwide. Bone marrow (BM)-derived stem cells promote tissue Repair and regeneration after MI. Thrombolytic treatment with plasminogen (Plg) activators significantly improves the clinical outcome in MI by restoration of Cardiac perfusion. In addition to its canonical function, Plg is critical for Cardiac Repair, wound healing and liver injury, however, the mechanism for Plg-regulated tissue Repair remains unclear. Here, we show a novel role of Plg in stem cell-mediated neovascularization and Cardiac Repair after MI. Our data show that Granulocyte colony-stimulating factor (G-CSF), a stem cell mobilizer, significantly increased neovascularization and decreased infarct size in the infarct area, and improved ejection fraction and LV internal diameter by echocardiogram in wild-type mice. No improvement in tissue Repair and heart function was observed in Plg deficient (Plg-/-) mice indicating that Plg is required for stem cell-regulated Cardiac Repair after MI. In vivo tracking of GFP-expressing BM cells after BM transplantation revealed that in Plg-/- mice, recruitment of BM-derived stem cells (GFP+c-kit+ cells) to the infarcted heart and stem cell-derived vessels and arteries are dramatically decreased (by 11 fold) suggesting that Plg may regulate stem cell homing to the lesion sites and subsequently contribute stem cell-mediated tissue regeneration. Mechanistic studies show that Plg up-regulated CXCR4 expression on stem cell in vivo and in vitro, suggesting Plg may promotes stem cell homing by induction of CXCR4 expression in stem cells. Stem cell migration was enhanced by endogenous Plg in vitro, however, AMD3100, a CXCR4 antagonist, significantly inhibited Plg-regulated stem cell migration. Furthermore, lentiviral reconstitution of CXCR4 expression in BM cells rescued stem cell homing to the infarcted heart in Plg-/- mice, indicating that Plg mediates stem cell homing through regulating CXCR4 expression. These findings identified a novel role of Plg in Cardiac Repair by promoting stem cell homing to the injured heart after MI. Thus, targeting Plg may offer a new therapeutic strategy for strengthening stem cell-mediated Cardiac Repair and regeneration after MI.

  • Plasminogen regulates Cardiac Repair after myocardial infarction through its noncanonical function in stem cell homing to the infarcted heart.
    Journal of the American College of Cardiology, 2014
    Co-Authors: Yanqing Gong, Yujing Zhao, Yi Fan, Jane Hoover-plow
    Abstract:

    The purpose of this study was to investigate the role of plasminogen (Plg) in stem cell-mediated Cardiac Repair and regeneration after myocardial infarction (MI). An MI induces irreversible tissue damage, eventually leading to heart failure. Bone marrow (BM)-derived stem cells promote tissue Repair and regeneration after MI. Thrombolytic treatment with Plg activators significantly improves the clinical outcome in MI by restoring Cardiac perfusion. However, the role of Plg in stem cell-mediated Cardiac Repair remains unclear. An MI was induced in Plg-deficient (Plg(-/-)) and wild-type (Plg(+/+)) mice by ligation of the left anterior descending coronary artery. Stem cells were visualized by in vivo tracking of green fluorescent protein (GFP)-expressing BM cells after BM transplantation. Cardiac function, stem cell homing, and signaling pathways downstream of Plg were examined. Granulocyte colony-stimulating factor, a stem cell mobilizer, significantly promoted BM-derived stem cell (GFP(+)c-kit(+) cell) recruitment into the infarcted heart and stem cell-mediated Cardiac Repair in Plg(+/+) mice. However, Plg deficiency markedly inhibited stem cell homing and Cardiac Repair, suggesting that Plg is critical for stem cell-mediated Cardiac Repair. Moreover, Plg regulated C-X-C chemokine receptor type 4 (CXCR4) expression in stem cells in vivo and in vitro through matrix metalloproteinase-9. Lentiviral reconstitution of CXCR4 expression in BM cells successfully rescued stem cell homing to the infarcted heart in Plg-deficient mice, indicating that CXCR4 has a critical role in Plg-mediated stem cell homing after MI. These findings have identified a novel role for Plg in stem cell-mediated Cardiac Repair after MI. Thus, targeting Plg may offer a new therapeutic strategy for stem cell-mediated Cardiac Repair after MI. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  • Plasminogen Regulates Cardiac Repair After Myocardial Infarction Through its Noncanonical Function in Stem Cell Homing to the Infarcted Heart
    Journal of the American College of Cardiology, 2014
    Co-Authors: Yanqing Gong, Yujing Zhao, Yi Fan, Jane Hoover-plow
    Abstract:

    Objectives The purpose of this study was to investigate the role of plasminogen (Plg) in stem cell–mediated Cardiac Repair and regeneration after myocardial infarction (MI). Background An MI induces irreversible tissue damage, eventually leading to heart failure. Bone marrow (BM)–derived stem cells promote tissue Repair and regeneration after MI. Thrombolytic treatment with Plg activators significantly improves the clinical outcome in MI by restoring Cardiac perfusion. However, the role of Plg in stem cell–mediated Cardiac Repair remains unclear. Methods An MI was induced in Plg-deficient (Plg −/− ) and wild-type (Plg +/+ ) mice by ligation of the left anterior descending coronary artery. Stem cells were visualized by in vivo tracking of green fluorescent protein (GFP)-expressing BM cells after BM transplantation. Cardiac function, stem cell homing, and signaling pathways downstream of Plg were examined. Results Granulocyte colony-stimulating factor, a stem cell mobilizer, significantly promoted BM-derived stem cell (GFP + c-kit + cell) recruitment into the infarcted heart and stem cell–mediated Cardiac Repair in Plg +/+ mice. However, Plg deficiency markedly inhibited stem cell homing and Cardiac Repair, suggesting that Plg is critical for stem cell–mediated Cardiac Repair. Moreover, Plg regulated C-X-C chemokine receptor type 4 (CXCR4) expression in stem cells in vivo and in vitro through matrix metalloproteinase-9. Lentiviral reconstitution of CXCR4 expression in BM cells successfully rescued stem cell homing to the infarcted heart in Plg-deficient mice, indicating that CXCR4 has a critical role in Plg-mediated stem cell homing after MI. Conclusions These findings have identified a novel role for Plg in stem cell–mediated Cardiac Repair after MI. Thus, targeting Plg may offer a new therapeutic strategy for stem cell–mediated Cardiac Repair after MI.

  • Abstract 197: Plasminogen Is Required for Hematopoietic Stem Cell-Mediated Cardiac Repair After Myocardial Infarction
    Circulation Research, 2012
    Co-Authors: Yanqing Gong, Jane Hoover-plow
    Abstract:

    Myocardial infarction (MI) is the primary cause of death throughout the United States. Granulocyte colony-stimulating factor (G-CSF) is used to mobilize hematopoietic progenitor and stem cells (HPSC) to improve Cardiac recovery after MI. However, poor-mobilization to G-CSF is observed in 25% of patients and 10-20% of healthy donors. Therefore, a better understanding of the underlying mechanisms may offer novel approaches for G-CSF-mediated therapeutics. Our previous studies have identified an essential role of Plg in HPSC mobilization from bone marrow (BM) in response to G-CSF. Here, we investigate the role of Plg in G-CSF-stimulated Cardiac Repair after MI. Our data show that G-CSF significantly improves Cardiac Repair including increasing neovascularization in the infarct area, and improving ejection fraction and LV internal diameter determined by echocardiogram in WT mice. No improvement on heart function is observed in Plg-/- mice, indicating Plg is required for G-CSF-regulated Cardiac Repair after MI...

  • Abstract 13: Plasminogen Is Required for Hematopoietic Stem Cell-Mediated Cardiac Repair After Myocardial Infarction
    Arteriosclerosis Thrombosis and Vascular Biology, 2012
    Co-Authors: Yanqing Gong, Jane Hoover-plow
    Abstract:

    Ischemic heart disease, including myocardial infarction (MI), is the primary cause of death throughout the US. Granulocyte colony-stimulating factor (G-CSF) is used to mobilize hematopoietic progenitor and stem cells (HPSC) to improve Cardiac recovery after MI. However, poor-mobilization to G-CSF is observed in 25% of patients and 10-20% of healthy donors. Therefore, a better understanding of the underlying mechanisms regulating G-CSF-induced Cardiac Repair may offer novel approaches for strengthening stem cell-mediated therapeutics. Our previous studies have identified an essential role of Plg in HPSC mobilization from bone marrow (BM) in response to G-CSF. Here, we investigate the role of Plg in G-CSF-stimulated Cardiac Repair after MI. Our data show that G-CSF significantly improves Cardiac tissue Repair including increasing neovascularization in the infarct area, and improving ejection fraction and LV internal diameter by echocardiogram in wild-type mice. No improvement in tissue Repair and heart func...

Mauricio Rojas - One of the best experts on this subject based on the ideXlab platform.

  • wnt1 βcatenin injury response activates the epicardium and Cardiac fibroblasts to promote Cardiac Repair
    The EMBO Journal, 2012
    Co-Authors: Jinzhu Duan, Costin M Gherghe, Dianxin Liu, Eric Hamlett, Luxman Srikantha, Laurel Rodgers, Jenna N Regan, Mauricio Rojas, Monte S Willis, Andrew Leask
    Abstract:

    Wnts are required for cardiogenesis but the role of specific Wnts in Cardiac Repair remains unknown. In this report, we show that a dynamic Wnt1/βcatenin injury response activates the epicardium and Cardiac fibroblasts to promote Cardiac Repair. Acute ischaemic Cardiac injury upregulates Wnt1 that is initially expressed in the epicardium and subsequently by Cardiac fibroblasts in the region of injury. Following Cardiac injury, the epicardium is activated organ‐wide in a Wnt‐dependent manner, expands, undergoes epithelial–mesenchymal transition (EMT) to generate Cardiac fibroblasts, which localize in the subepicardial space. The injured regions in the heart are Wnt responsive as well and Wnt1 induces Cardiac fibroblasts to proliferate and express pro‐fibrotic genes. Disruption of downstream Wnt signalling in epicardial cells decreases epicardial expansion, EMT and leads to impaired Cardiac function and ventricular dilatation after Cardiac injury. Furthermore, disruption of Wnt/βcatenin signalling in Cardiac fibroblasts impairs wound healing and decreases Cardiac performance as well. These findings reveal that a pro‐fibrotic Wnt1/βcatenin injury response is critically required for preserving Cardiac function after acute ischaemic Cardiac injury.

  • Wnt1/βcatenin injury response activates the epicardium and Cardiac fibroblasts to promote Cardiac Repair
    The EMBO Journal, 2011
    Co-Authors: Jinzhu Duan, Costin M Gherghe, Dianxin Liu, Eric Hamlett, Luxman Srikantha, Laurel Rodgers, Jenna N Regan, Mauricio Rojas, Monte S Willis, Andrew Leask
    Abstract:

    Wnts are required for cardiogenesis but the role of specific Wnts in Cardiac Repair remains unknown. In this report, we show that a dynamic Wnt1/βcatenin injury response activates the epicardium and Cardiac fibroblasts to promote Cardiac Repair. Acute ischaemic Cardiac injury upregulates Wnt1 that is initially expressed in the epicardium and subsequently by Cardiac fibroblasts in the region of injury. Following Cardiac injury, the epicardium is activated organ‐wide in a Wnt‐dependent manner, expands, undergoes epithelial–mesenchymal transition (EMT) to generate Cardiac fibroblasts, which localize in the subepicardial space. The injured regions in the heart are Wnt responsive as well and Wnt1 induces Cardiac fibroblasts to proliferate and express pro‐fibrotic genes. Disruption of downstream Wnt signalling in epicardial cells decreases epicardial expansion, EMT and leads to impaired Cardiac function and ventricular dilatation after Cardiac injury. Furthermore, disruption of Wnt/βcatenin signalling in Cardiac fibroblasts impairs wound healing and decreases Cardiac performance as well. These findings reveal that a pro‐fibrotic Wnt1/βcatenin injury response is critically required for preserving Cardiac function after acute ischaemic Cardiac injury.

  • Abstract 20118: Wnt1 Mediated Dynamic Injury Response Activates the Epicardium and is Critical for Mammalian Cardiac Repair
    Circulation, 2010
    Co-Authors: Arjun Deb, Costin M Gherghe, Dianxin Liu, Eric Hamlett, Jenna N Regan, Luxman Srikanth, Biplab Giri, Laurel S. Rodgers, Jackie Kylander, Mauricio Rojas
    Abstract:

    The epicardium is activated following acute Cardiac injury in zebrafish and plays a critical role in heart regeneration. The role of the mammalian epicardium in Cardiac Repair is unknown. The Wnt s...

Jinzhu Duan - One of the best experts on this subject based on the ideXlab platform.

  • wnt1 βcatenin injury response activates the epicardium and Cardiac fibroblasts to promote Cardiac Repair
    The EMBO Journal, 2012
    Co-Authors: Jinzhu Duan, Costin M Gherghe, Dianxin Liu, Eric Hamlett, Luxman Srikantha, Laurel Rodgers, Jenna N Regan, Mauricio Rojas, Monte S Willis, Andrew Leask
    Abstract:

    Wnts are required for cardiogenesis but the role of specific Wnts in Cardiac Repair remains unknown. In this report, we show that a dynamic Wnt1/βcatenin injury response activates the epicardium and Cardiac fibroblasts to promote Cardiac Repair. Acute ischaemic Cardiac injury upregulates Wnt1 that is initially expressed in the epicardium and subsequently by Cardiac fibroblasts in the region of injury. Following Cardiac injury, the epicardium is activated organ‐wide in a Wnt‐dependent manner, expands, undergoes epithelial–mesenchymal transition (EMT) to generate Cardiac fibroblasts, which localize in the subepicardial space. The injured regions in the heart are Wnt responsive as well and Wnt1 induces Cardiac fibroblasts to proliferate and express pro‐fibrotic genes. Disruption of downstream Wnt signalling in epicardial cells decreases epicardial expansion, EMT and leads to impaired Cardiac function and ventricular dilatation after Cardiac injury. Furthermore, disruption of Wnt/βcatenin signalling in Cardiac fibroblasts impairs wound healing and decreases Cardiac performance as well. These findings reveal that a pro‐fibrotic Wnt1/βcatenin injury response is critically required for preserving Cardiac function after acute ischaemic Cardiac injury.

  • Wnt1/βcatenin injury response activates the epicardium and Cardiac fibroblasts to promote Cardiac Repair
    The EMBO Journal, 2011
    Co-Authors: Jinzhu Duan, Costin M Gherghe, Dianxin Liu, Eric Hamlett, Luxman Srikantha, Laurel Rodgers, Jenna N Regan, Mauricio Rojas, Monte S Willis, Andrew Leask
    Abstract:

    Wnts are required for cardiogenesis but the role of specific Wnts in Cardiac Repair remains unknown. In this report, we show that a dynamic Wnt1/βcatenin injury response activates the epicardium and Cardiac fibroblasts to promote Cardiac Repair. Acute ischaemic Cardiac injury upregulates Wnt1 that is initially expressed in the epicardium and subsequently by Cardiac fibroblasts in the region of injury. Following Cardiac injury, the epicardium is activated organ‐wide in a Wnt‐dependent manner, expands, undergoes epithelial–mesenchymal transition (EMT) to generate Cardiac fibroblasts, which localize in the subepicardial space. The injured regions in the heart are Wnt responsive as well and Wnt1 induces Cardiac fibroblasts to proliferate and express pro‐fibrotic genes. Disruption of downstream Wnt signalling in epicardial cells decreases epicardial expansion, EMT and leads to impaired Cardiac function and ventricular dilatation after Cardiac injury. Furthermore, disruption of Wnt/βcatenin signalling in Cardiac fibroblasts impairs wound healing and decreases Cardiac performance as well. These findings reveal that a pro‐fibrotic Wnt1/βcatenin injury response is critically required for preserving Cardiac function after acute ischaemic Cardiac injury.

Costin M Gherghe - One of the best experts on this subject based on the ideXlab platform.

  • wnt1 βcatenin injury response activates the epicardium and Cardiac fibroblasts to promote Cardiac Repair
    The EMBO Journal, 2012
    Co-Authors: Jinzhu Duan, Costin M Gherghe, Dianxin Liu, Eric Hamlett, Luxman Srikantha, Laurel Rodgers, Jenna N Regan, Mauricio Rojas, Monte S Willis, Andrew Leask
    Abstract:

    Wnts are required for cardiogenesis but the role of specific Wnts in Cardiac Repair remains unknown. In this report, we show that a dynamic Wnt1/βcatenin injury response activates the epicardium and Cardiac fibroblasts to promote Cardiac Repair. Acute ischaemic Cardiac injury upregulates Wnt1 that is initially expressed in the epicardium and subsequently by Cardiac fibroblasts in the region of injury. Following Cardiac injury, the epicardium is activated organ‐wide in a Wnt‐dependent manner, expands, undergoes epithelial–mesenchymal transition (EMT) to generate Cardiac fibroblasts, which localize in the subepicardial space. The injured regions in the heart are Wnt responsive as well and Wnt1 induces Cardiac fibroblasts to proliferate and express pro‐fibrotic genes. Disruption of downstream Wnt signalling in epicardial cells decreases epicardial expansion, EMT and leads to impaired Cardiac function and ventricular dilatation after Cardiac injury. Furthermore, disruption of Wnt/βcatenin signalling in Cardiac fibroblasts impairs wound healing and decreases Cardiac performance as well. These findings reveal that a pro‐fibrotic Wnt1/βcatenin injury response is critically required for preserving Cardiac function after acute ischaemic Cardiac injury.

  • Wnt1/βcatenin injury response activates the epicardium and Cardiac fibroblasts to promote Cardiac Repair
    The EMBO Journal, 2011
    Co-Authors: Jinzhu Duan, Costin M Gherghe, Dianxin Liu, Eric Hamlett, Luxman Srikantha, Laurel Rodgers, Jenna N Regan, Mauricio Rojas, Monte S Willis, Andrew Leask
    Abstract:

    Wnts are required for cardiogenesis but the role of specific Wnts in Cardiac Repair remains unknown. In this report, we show that a dynamic Wnt1/βcatenin injury response activates the epicardium and Cardiac fibroblasts to promote Cardiac Repair. Acute ischaemic Cardiac injury upregulates Wnt1 that is initially expressed in the epicardium and subsequently by Cardiac fibroblasts in the region of injury. Following Cardiac injury, the epicardium is activated organ‐wide in a Wnt‐dependent manner, expands, undergoes epithelial–mesenchymal transition (EMT) to generate Cardiac fibroblasts, which localize in the subepicardial space. The injured regions in the heart are Wnt responsive as well and Wnt1 induces Cardiac fibroblasts to proliferate and express pro‐fibrotic genes. Disruption of downstream Wnt signalling in epicardial cells decreases epicardial expansion, EMT and leads to impaired Cardiac function and ventricular dilatation after Cardiac injury. Furthermore, disruption of Wnt/βcatenin signalling in Cardiac fibroblasts impairs wound healing and decreases Cardiac performance as well. These findings reveal that a pro‐fibrotic Wnt1/βcatenin injury response is critically required for preserving Cardiac function after acute ischaemic Cardiac injury.

  • Abstract 20118: Wnt1 Mediated Dynamic Injury Response Activates the Epicardium and is Critical for Mammalian Cardiac Repair
    Circulation, 2010
    Co-Authors: Arjun Deb, Costin M Gherghe, Dianxin Liu, Eric Hamlett, Jenna N Regan, Luxman Srikanth, Biplab Giri, Laurel S. Rodgers, Jackie Kylander, Mauricio Rojas
    Abstract:

    The epicardium is activated following acute Cardiac injury in zebrafish and plays a critical role in heart regeneration. The role of the mammalian epicardium in Cardiac Repair is unknown. The Wnt s...