Endothelial Cell Function and Dysfunction in Critically Ill Children

Pierce, Richard W.; Giuliano, John S.; Pober, Jordan S.

doi:10.1542/peds.2017-0355

Cited by 26 publications

(35 citation statements)

References 82 publications

(59 reference statements)

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“…Endothelial glycocalyx degradation occurs in chronic disease states like diabetes mellitus [13], significantly impacting responses to acute infectious and metabolic conditions [14,15] (Fig. 4).…”

Section: Vascular Endothelial Glycocalyxmentioning

confidence: 99%

COVID-19-associated vasculitis and vasculopathy

Becker

2020

J Thromb Thrombolysis

240

259

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The COVID-19 pandemic now totaling 13,000,000 cases and over 571,000 deaths has continued to teach the medical, scientific and lay communities about viral infectious disease in the modern era. Among the many lessons learned for the medical community is the potential for transmissibility and host infectivity of the SARS-CoV-2 virus. Moreover, it has become clear that the virus can affect any organ including the circulatory system, directly via either tissue tropism or indirectly stemming from inflammatory responses in the form of innate immunity, leukocyte debris such as cell-free DNA and histones and RNA viral particles. The following review considers COVID-19-associated vasculitis and vasculopathy as a defining feature of a virus-induced systemic disease with acute, subacute and potential chronic health implications.

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Section: Vascular Endothelial Glycocalyxmentioning

confidence: 99%

COVID-19-associated vasculitis and vasculopathy

Becker

2020

J Thromb Thrombolysis

240

259

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“…This switch is characterized by three major components: EC dysfunction, destruction, and impaired repair. Based on the data summarized below from studies in obese, asymptomatic and obese, critically ill populations, it is plausible that obesity and obesity-associated chronic inflammation, oxidative stress, and insulin resistance (IR) may intensify EA and, in turn, contribute to worse outcomes among obese, critically ill children ( 17 ). Extreme nutrient excess may cause obese adipocyte cell death resulting in cytokine and fatty acid release.…”

Section: Endothelial Activationmentioning

confidence: 99%

“…Activation of protein kinases such as PKR, as in IR, may inhibit PI-3K activity and eNOS expression ( 22 ). Superimposition of critical illness such as sepsis, acute respiratory distress syndrome (ARDS), multiple-organ dysfunction syndrome (MODS), trauma, and cardiopulmonary bypass (CPB) for cardiac surgery may compound the effects of obesity by further overwhelming these pathways ( 17 ).…”

Section: Endothelial Activationmentioning

confidence: 99%

“…Adhesion molecules such as E-selectin are significantly higher in septic children with >3 failed organ systems compared to those with ≤ 3 failed organ systems, suggesting a role in EA ( 73 ). Pro-inflammatory markers, specifically IL-1, IL-6, and tumor necrosis factor, activate ECs to produce and express adhesion molecules (ICAM-1, E-selectin) to promote leukocyte motility and adhesion in the systemic inflammatory response ( 17 ). Derangements in endothelial and inflammatory biomarkers (higher VEGF, thrombomodulin, CRP, IL-6, IL-8) were shown in children upon presentation to the ICU with extrapulmonary sepsis with and without ARDS ( 74 ).…”

Section: Obesity-associated Endothelial Activationmentioning

confidence: 99%

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Childhood Obesity, Endothelial Cell Activation, and Critical Illness

Radman¹,

McGuire²,

Zimmerman³

2020

Front. Pediatr.

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Pediatric obesity is increasing in prevalence and is frequently an antecedent to adult obesity and adult obesity-associated morbidities such as atherosclerosis, type II diabetes, and chronic metabolic syndrome. Endothelial cell activation, one aspect of inflammation, is present in the early stages of atherosclerosis, often prior to the onset of symptoms. Endothelial activation is a pathological condition in which vasoconstricting, pro-thrombotic, and proliferative mediators predominate protective vasodilating, anti-thrombogenic, and anti-mitogenic mediators. Many studies report poor outcomes among obese children with systemic endothelial activation. Likewise, the link between childhood obesity and poor outcomes in critical illness is well-established. However, the link between obesity and severity of endothelial activation specifically in the setting of critical illness is largely unstudied. Although endothelial cell activation is believed to worsen disease in critically ill children, the nature and extent of this response is poorly understood due to the difficulty in measuring endothelial cell dysfunction and destruction. Based on the data available for the obese, asymptomatic population and the obese, critically ill population, the authors posit that obesity, and obesity-associated chronic inflammation, including oxidative stress and insulin resistance, may contribute to endothelial activation and associated worse outcomes among critically ill children. A research agenda to examine this hypothesis is suggested.

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“…A widely-held general explanation is that exposure of the patient’s circulating blood cells to the artificial surfaces of the bypass circuit, combined with parenchymal ischemia-reperfusion injury, induces a systemic inflammatory response that includes release of variety of soluble mediators in serum(3–14). Some of the identified mediators, such as angiopoietin-2 (angpt-2) and tumor necrosis factor (TNF), are known to act on cultured ECs to destabilize barriers, directly and via new gene expression (dependent upon the transcription factor NF-κB) (15, 16). Such studies have not been particularly revealing of pathologic changes in EC associated with post-CPB leak.…”

Section: Introductionmentioning

confidence: 99%