Endothelial Cell Regulation of Pulmonary Vascular Tone, Inflammation, and Coagulation

Goldenberg, Neil M.; Kuebler, Wolfgang M.

doi:10.1002/cphy.c140024

Cited by 46 publications

(41 citation statements)

References 269 publications

(300 reference statements)

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“…15). As an integral component of the alveolar-capillary unit, it is structurally and functionally optimised to facilitate perfusion-ventilation matching.…”

Section: Structure and Function Of The Pulmonary Endotheliummentioning

confidence: 99%

The pulmonary endothelium in acute respiratory distress syndrome: insights and therapeutic opportunities

Millar

Summers

Griffiths

et al. 2016

Thorax

189

181

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The pulmonary endothelium is a dynamic, metabolically active layer of squamous endothelial cells ideally placed to mediate key processes involved in lung homoeostasis. Many of these are disrupted in acute respiratory distress syndrome (ARDS), a syndrome with appreciable mortality and no effective pharmacotherapy. In this review, we consider the role of the pulmonary endothelium as a key modulator and orchestrator of ARDS, highlighting advances in our understanding of endothelial pathobiology and their implications for the development of endothelial-targeted therapeutics including cell-based therapies. We also discuss mechanisms to facilitate the translation of preclinical data into effective therapies including the application of biomarkers to phenotype patients with ARDS with a predominance of endothelial injury and emerging biotechnologies that could enhance delivery, discovery and testing of lung endothelial-specific therapeutics.

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“…15). As an integral component of the alveolar-capillary unit, it is structurally and functionally optimised to facilitate perfusion-ventilation matching.…”

Section: Structure and Function Of The Pulmonary Endotheliummentioning

confidence: 99%

The pulmonary endothelium in acute respiratory distress syndrome: insights and therapeutic opportunities

Millar

Summers

Griffiths

et al. 2016

Thorax

189

181

View full text Add to dashboard Cite

show abstract

“…The pulmonary vasculature is critical to gas exchange in the lung, with a total pulmonary vascular surface area of 90m 2 [9]. The entire vascular system is lined by endothelial cells which form a continuous monolayer [9].…”

Section: Introductionmentioning

confidence: 99%

“…The entire vascular system is lined by endothelial cells which form a continuous monolayer [9]. Endothelial cells are encased by a basement membrane, a thin protein sheet (50nm thick) that consists of laminins, collagen and proteoglycans [10].…”

Section: Introductionmentioning

confidence: 99%

The role of the endothelium in asthma and chronic obstructive pulmonary disease (COPD)

Green

Turner

2017

Respir Res

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COPD and asthma are important chronic inflammatory disorders with a high associated morbidity. Much research has concentrated on the role of inflammatory cells, such as the neutrophil, in these diseases, but relatively little focus has been given to the endothelial tissue, through which inflammatory cells must transmigrate to reach the lung parenchyma and cause damage. There is evidence that there is an abnormal amount of endothelial tissue in COPD and asthma and that this tissue and its’ progenitor cells behave in a dysfunctional manner. This article reviews the evidence of the involvement of pulmonary endothelium in COPD and asthma and potential treatment options for this.

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“…In contrast to this flow-facilitating role of normal endothelium, in sites of vascular damage, endothelial cells instead support clotting, with the teleological goal of preventing bleeding [44,45]. In this role, endothelial cells expose pro-coagulant molecules phosphatidyl serine (PS), inhibitors of plasmin and its activators, and release glycoproteins that stimulate blood clotting and platelet activation, such as von Willebrand factor and P-selectin from intracellular stores (Weibel-Palade bodies).…”

Section: Vascular Endotheliummentioning

confidence: 99%

Targeted endothelial nanomedicine for common acute pathological conditions

Shuvaev

Brenner

Muzykantov

2015

Journal of Controlled Release

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Endothelium, a thin monolayer of specialized cells lining the lumen of blood vessels is the key regulatory interface between blood and tissues. Endothelial abnormalities are implicated in many diseases, including common acute conditions with high morbidity and mortality lacking therapy, in part because drugs and drug carriers have no natural endothelial affinity. Precise endothelial drug delivery may improve management of these conditions. Using ligands of molecules exposed to the bloodstream on the endothelial surface enables design of diverse targeted endothelial nanomedicine agents. Target molecules and binding epitopes must be accessible to drug carriers, carriers must be free of harmful effects, and targeting should provide desirable sub-cellular addressing of the drug cargo. The roster of current candidate target molecules for endothelial nanomedicine includes peptidases and other enzymes, cell adhesion molecules and integrins, localized in different domains of the endothelial plasmalemma and differentially distributed throughout the vasculature. Endowing carriers with an affinity to specific endothelial epitopes enables an unprecedented level of precision of control of drug delivery: binding to selected endothelial cell phenotypes, cellular addressing and duration of therapeutic effects. Features of nanocarrier design such as choice of epitope and ligand control delivery and effect of targeted endothelial nanomedicine agents. Pathological factors modulate endothelial targeting and uptake of nanocarriers. Selection of optimal binding sites and design features of nanocarriers are key controllable factors that can be iteratively engineered based on their performance from in vitro to pre-clinical in vivo experimental models. Targeted endothelial nanomedicine agents provide antioxidant, anti-inflammatory and other therapeutic effects unattainable by non-targeted counterparts in animal models of common acute severe human disease conditions. The results of animal studies provide the basis for the challenging translation endothelial nanomedicine into the clinical domain.

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Endothelial Cell Regulation of Pulmonary Vascular Tone, Inflammation, and Coagulation

Cited by 46 publications

References 269 publications

The pulmonary endothelium in acute respiratory distress syndrome: insights and therapeutic opportunities

The pulmonary endothelium in acute respiratory distress syndrome: insights and therapeutic opportunities

The role of the endothelium in asthma and chronic obstructive pulmonary disease (COPD)

Targeted endothelial nanomedicine for common acute pathological conditions

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