The neuropeptide galanin promotes an anti-thrombotic phenotype on endocardial endothelial cells from heart failure patients

Christina Tyrrell, Amanda Toyooka, Faiza Khan, Kent Thornburg, James Mudd, Wohaib Hasan

    Research output: Contribution to journalArticle

    2 Citations (Scopus)

    Abstract

    Thromboembolic complications are a significant cause of mortality and re-hospitalization in heart failure (HF) patients. One source of thrombi is the ventricular endocardial surface that becomes increasingly pro-thrombotic as HF progresses. Anticoagulation comes with bleeding risks so identifying therapeutic agents for improving cardiac endothelial health are of critical clinical importance. Endocardial endothelial cells are closely apposed to cardiac sympathetic nerves. In HF, cardiac sympathetic nerves are dysregulated and promote disease progression. Whether endocardial endothelial health and function is impacted by sympathetic dysregulation in HF is unknown. Also unexplored is the impact of neuropeptides, such as galanin and neuropeptide Y (NPY), co-released from sympathetic nerve terminals, on endothelial health. In this study we examined the effect of sympathetic nerve-released neurotransmitters and neuropeptides on the procoagulant phenotype of cultured human endocardial endothelial cells from HF patients. As a functional readout of procoagulant state we examined thrombin-mediated von Willebrand factor (vWF) extrusion and multimer expression. We demonstrate that vWF extrusion and multimer expression is promoted by thrombin, that isoproterenol (a beta-adrenergic receptor agonist) augments this effect, whereas co-treatment with the beta-blockers propranolol and carvedilol blocks this effect. We also show that vWF extrusion and multimer expression is attenuated by treatment with the neuropeptide galanin, but not with NPY. Our results are consistent with a protective role of beta-blockers and galanin on endocardial endothelial health in heart failure. Improving endothelial health through galanin therapy is a future clinical application of this study.

    Original languageEnglish (US)
    Pages (from-to)35-42
    Number of pages8
    JournalAutonomic Neuroscience: Basic and Clinical
    Volume206
    DOIs
    StatePublished - Sep 1 2017

    Fingerprint

    Galanin
    Neuropeptides
    Endothelial Cells
    Heart Failure
    Phenotype
    von Willebrand Factor
    Health
    Neuropeptide Y
    Thrombin
    Adrenergic beta-Agonists
    Therapeutics
    Isoproterenol
    Propranolol
    Neurotransmitter Agents
    Disease Progression
    Hospitalization
    Thrombosis
    Hemorrhage
    Mortality

    Keywords

    • Autonomic
    • Endocardial endothelial cells
    • Heart failure
    • Neuropeptides
    • Sympathetic
    • Thrombosis
    • von Willebrand factor

    ASJC Scopus subject areas

    • Endocrine and Autonomic Systems
    • Clinical Neurology
    • Cellular and Molecular Neuroscience

    Cite this

    The neuropeptide galanin promotes an anti-thrombotic phenotype on endocardial endothelial cells from heart failure patients. / Tyrrell, Christina; Toyooka, Amanda; Khan, Faiza; Thornburg, Kent; Mudd, James; Hasan, Wohaib.

    In: Autonomic Neuroscience: Basic and Clinical, Vol. 206, 01.09.2017, p. 35-42.

    Research output: Contribution to journalArticle

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