Jamie E. Meegan

Jamie E. Meegan
Vanderbilt University | Vander Bilt · Division of Allergy, Pulmonary and Critical Care

Doctor of Philosophy
Postdoctoral Research Fellow at VUMC

About

35
Publications
2,549
Reads
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385
Citations
Citations since 2017
30 Research Items
385 Citations
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2017201820192020202120222023020406080100
2017201820192020202120222023020406080100
Introduction
Microvascular physiologist interested in the regulation of endothelial function and dysfunction in health and disease. Currently a Postdoctoral Research Fellow at Vanderbilt University Medical Center investigating the effects of cell-free hemoglobin on microvascular endothelial barrier dysfunction during sepsis and acute respiratory distress syndrome.
Education
August 2013 - May 2018
University of South Florida
Field of study
  • Medical Sciences - Cardiovascular Biology
August 2009 - May 2013
Trine University
Field of study
  • Chemistry

Publications

Publications (35)
Article
Cell-free hemoglobin is a pathophysiological driver of endothelial injury during sepsis and acute respiratory distress syndrome (ARDS), but the precise mechanisms are not fully understood. We hypothesized that hemoglobin (Hb) increases leukocyte adhesion and endothelial activation in human lung microvascular endothelial cells (HLMVEC). We stimulate...
Article
Full-text available
Circulating cell‐free hemoglobin (CFH) is elevated in pulmonary arterial hypertension (PAH) and associated with poor outcomes but the mechanisms are unknown. We hypothesized that CFH is generated from the pulmonary circulation and inadequately cleared in PAH. Transpulmonary CFH (difference between wedge and pulmonary artery positions) and lung hemo...
Article
Full-text available
Sepsis is a devastating disease with high morbidity and mortality and no specific treatments. The pathophysiology of sepsis involves a hyperinflammatory response and release of damage-associated molecular patterns (DAMPs), including adenosine triphosphate (ATP), from activated and dying cells. Purinergic receptors activated by ATP have gained atten...
Article
Sepsis is a critical problem in intensive care units globally, and accounts for 20% of all annual deaths. During septic shock, the highly inflammatory state leads to the release of cell-free hemoglobin (CFH) from lysed red blood cells. Once released into the vascular circulation, CFH can oxidize from the normal ferrous 2+ state to methemoglobin (3+...
Article
Introduction: Sepsis, a dysregulated host response to infection with high morbidity and mortality, is characterized by a systemic inflammatory response and widespread vascular hyperpermeability leading to edema, organ dysfunction, and death with no specific treatments. Disruption of the microvascular endothelial barrier is a critical pathological...
Article
Mouse models of acute lung injury (ALI) have been instrumental for studies of the biologic underpinnings of lung inflammation and permeability, but murine models of sepsis generate minimal lung injury. Our goal was to create a murine sepsis model of ALI that reflects the inflammation, lung edema, histologic abnormalities and physiologic dysfunction...
Article
Circulating cell-free hemoglobin (CFH) contributes to endothelial injury in several inflammatory and hemolytic conditions. We and others have shown that CFH causes increased endothelial permeability, but the precise mechanisms of CFH-mediated endothelial barrier dysfunction are not fully understood. Based on our previous study in a mouse model of s...
Article
Levels of circulating cell-free hemoglobin are elevated during hemolytic and inflammatory diseases and contribute to organ dysfunction and severity of illness. Though several studies have investigated the contribution of hemoglobin to tissue injury, the precise signaling mechanisms of hemoglobin-mediated endothelial dysfunction in the lung and othe...
Article
Non-invasive sampling of the distal airspace in patients with Acute Respiratory Distress Syndrome (ARDS) has long eluded clinical and translational researchers. We recently reported that fluid collected from Heat Moisture Exchange filters (HME) closely mirrors fluid directly aspirated from the distal airspace. In the current study, we sought to det...
Article
Full-text available
Objectives We previously reported microvascular leakage resulting from fibrinogen-γ chain C-terminal products (γC) occurred via a RhoA-dependent mechanism. The objective of this study was to further elucidate the signaling mechanism by which γC induces endothelial hyperpermeability. Since it is known that γC binds and activates endothelial αvβ3, a...
Article
Full-text available
Increased endothelial permeability is central to the pathogenesis of sepsis and leads to organ dysfunction and death but the endogenous mechanisms that drive increased endothelial permeability are not completely understood. We previously reported that cell-free hemoglobin (CFH), elevated in 80% of patients with sepsis, increases lung microvascular...
Article
Full-text available
Aims: Microvesicles (MVs) conduct intercellular communication and impact diverse biological processes by transferring bioactive cargos to other cells. We investigated whether and how endothelial production of MVs contribute to vascular dysfunction during inflammation. Methods and results: We measured the levels and molecular properties of endoth...
Article
Full-text available
Objective The endothelial glycocalyx constitutes part of the endothelial barrier but its degradation leaves endothelial cells exposed to transmigrating cells and circulating mediators that can damage the barrier or promote intercellular gaps. Syndecan proteins are key components of the endothelial glycocalyx and are shed during disease states where...
Article
Full-text available
The microvascular endothelium serves as the major barrier that controls the transport of blood constituents across the vessel wall. Barrier leakage occurs during infection or sterile inflammation, allowing plasma fluid and cells to extravasate and accumulate in surrounding tissues, an important pathology underlying a variety of infectious diseases...
Article
Inflammation-induced blood–brain barrier (BBB) dysfunction and microvascular leakage are associated with a host of neurological disorders. The tight junction protein claudin-5 (CLDN5) is a crucial protein necessary for BBB integrity and maintenance. CLDN5 is negatively regulated by the transcriptional repressor FOXO1, whose activity increases durin...
Article
Full-text available
Aims: Endothelial hyperpermeability exacerbates multiple organ damage during inflammation or infection. The endothelial glycocalyx, a protective matrix covering the luminal surface of endothelial cells (ECs), undergoes enzymatic shedding during inflammation, contributing to barrier hyperpermeability. A disintegrin and metalloproteinase 15 (ADAM15)...
Article
Neutrophils play an essential role in host defense against infection or injury. While neutrophil activation is necessary for pathogen clearance and tissue repair, a hyperactive response can lead to tissue damage and microcirculatory disorders, a process involving complex neutrophil-endothelium crosstalk. This review highlights recent research findi...
Article
Full-text available
Endothelial dysfunction is a hallmark of systemic inflammatory response underlying multiple organ failure. Here we report a novel function of DHHC-containing palmitoyl acyltransferases (PATs) in mediating endothelial inflammation. Pharmacological inhibition of PATs attenuates barrier leakage and leucocyte adhesion induced by endothelial junction hy...
Data
Supplementary Figures 1-5 and Supplementary Tables 1-7.
Poster
Neutrophil extracellular traps (NETs) participate in host defense against infection. Increased levels of NETs have been detected in patients with systemic inflammatory response syndrome (SIRS). Furthermore, several animal models of SIRS have shown that circulating NETs exacerbate vascular injury in inflammation. The purpose of this study was to det...
Article
Blood-brain barrier (BBB) dysfunction is a hallmark of neuroinflammation brought on by pathologies such as stroke and amyloid angiopathy. Inflammatory cytokines that act directly on cerebral endothelium can impair tight junction (TJ) stability. We previously identified a mechanism for IL-1β-mediated dysfunction involving inactivation of the PI3K/Ak...
Poster
Full-text available
Blood-brain barrier (BBB) dysfunction is a hallmark of neuroinflammation brought on by pathologies such as stroke and amyloid angiopathy. Inflammatory cytokines that act directly on cerebral endothelium can impair tight junction (TJ) stability. We previously identified a mechanism for IL-1β-mediated dysfunction involving inactivation of the PI3K/Ak...

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Projects

Project (1)
Project
Determine the effects of NETs and NET components on vascular endothelial barrier injury during inflammatory conditions like sepsis.