A Razor's Edge: Vascular Responses to Acute Inflammatory Lung Injury/Acute Respiratory Distress Syndrome

Abstract

Historically considered a metabolically inert cellular layer separating the blood from the underlying tissue, the endothelium is now recognized as a highly dynamic, metabolically active tissue that is critical to organ homeostasis. Under homeostatic conditions, lung endothelial cells (ECs) in healthy subjects are quiescent, promoting vasodilation, platelet disaggregation, and anti-inflammatory mechanisms. In contrast, lung ECs are essential contributors to the pathobiology of acute respiratory distress syndrome (ARDS), as the quiescent endothelium is rapidly and radically altered upon exposure to environmental stressors, infectious pathogens, or endogenous danger signals into an effective and formidable regulator of innate and adaptive immunity. These dramatic perturbations, produced in a tsunami of inflammatory cascade activation, result in paracellular gap formation between lung ECs, sustained lung edema, and multi-organ dysfunction that drives ARDS mortality. The astonishing plasticity of the lung endothelium in negotiating this inflammatory environment and efforts to therapeutically target the aberrant ARDS endothelium are examined in further detail in this review.

Serum from patients with cirrhosis undergoing liver transplantation induces permeability in human pulmonary microvascular endothelial cells ex vivo

“…Shortly after liver graft reperfusion, LT sera induced more HPMEC permeability than at baseline, suggesting that IR of the liver graft further reduces endothelial barrier function. Postreperfusion effects on the endothelium may contribute to patient outcomes after LT. Disruption of the endothelial barrier may directly lead to tissue edema and organ failure ( 22 , 23 ). Patient and graft outcomes are significantly worse when these organ injuries complicate LT ( 24 , 25 ).…”

“…The resultant interstitial edema may contribute to acute kidney injury ( 23 ). Acute respiratory distress syndrome, a common complication of sepsis and trauma, is characterized by profound disruption of the endothelial barrier and persistent lung edema ( 22 ). Traumatic shock ( 13 ) and COVID-19 infection ( 14 ) also increase endothelial permeability in ex vivo models.…”