Endothelial Metabolism in Pulmonary Vascular Homeostasis and Acute Respiratory Distress Syndrome

2021 ◽  
Author(s):  
Reece P Stevens ◽  
Sunita S. Paudel ◽  
Santina C Johnson ◽  
Troy Stevens ◽  
Ji Young Lee
Keyword(s):  
Endothelial Cells ◽  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Epigenetic Landscape ◽  
Pulmonary Capillary ◽  
Capillary Endothelial Cells ◽  
Insight Into ◽  
Alveolar Capillary

Capillary endothelial cells possess a specialized metabolism necessary to adapt to the unique alveolar-capillary environment. Here, we highlight how endothelial metabolism preserves the integrity of the pulmonary circulation by controlling vascular permeability, defending against oxidative stress, facilitating rapid migration and angiogenesis in response to injury, and regulating the epigenetic landscape of endothelial cells. Recent reports on single cell RNA sequencing reveal subpopulations of pulmonary capillary endothelial cells with distinctive reparative capacities which potentially offers new insight into their metabolic signature. Lastly, we discuss broad implications of pulmonary vascular metabolism on acute respiratory distress syndrome, touching on emerging findings of endotheliitis in Coronavirus Disease 2019 (COVID-19) lungs.

α1-Antitrypsin: Key Player or Bystander in Acute Respiratory Distress Syndrome?

2021 ◽  
Vol 134 (5) ◽  
pp. 792-808
Author(s):  
Grace Hogan ◽  
Pierce Geoghegan ◽  
Tomás P. Carroll ◽  
Jennifer Clarke ◽  
Oisín F. McElvaney ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Main Function ◽  
Alveolar Capillary ◽  
Target Effects ◽  
Antiprotease Activity ◽  
The Ideal

Acute respiratory distress syndrome is characterized by hypoxemia, altered alveolar–capillary permeability, and neutrophil-dominated inflammatory pulmonary edema. Despite decades of research, an effective drug therapy for acute respiratory distress syndrome remains elusive. The ideal pharmacotherapy for acute respiratory distress syndrome should demonstrate antiprotease activity and target injurious inflammatory pathways while maintaining host defense against infection. Furthermore, a drug with a reputable safety profile, low possibility of off-target effects, and well-known pharmacokinetics would be desirable. The endogenous 52-kd serine protease α1-antitrypsin has the potential to be a novel treatment option for acute respiratory distress syndrome. The main function of α1-antitrypsin is as an antiprotease, targeting neutrophil elastase in particular. However, studies have also highlighted the role of α1-antitrypsin in the modulation of inflammation and bacterial clearance. In light of the current SARS-CoV-2 pandemic, the identification of a treatment for acute respiratory distress syndrome is even more pertinent, and α1-antitrypsin has been implicated in the inflammatory response to SARS-CoV-2 infection.

scholarly journals Insight into erythrocyte phospholipid molecular flux in healthy humans and in patients with acute respiratory distress syndrome

PLoS ONE ◽  
2019 ◽  
Vol 14 (8) ◽  
pp. e0221595 ◽  
Author(s):  
Ahilanandan Dushianthan ◽  
Rebecca Cusack ◽  
Grielof Koster ◽  
Michael P. W. Grocott ◽  
Anthony D. Postle
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Healthy Humans ◽  
Molecular Flux ◽  
Insight Into

scholarly journals Kallikrein-kinin blockade in patients with COVID-19 to prevent acute respiratory distress syndrome

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Frank L van de Veerdonk ◽  
Mihai G Netea ◽  
Marcel van Deuren ◽  
Jos WM van der Meer ◽  
Quirijn de Mast ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Pulmonary Edema ◽  
Distress Syndrome ◽  
Vascular Leakage ◽  
Plasma Kallikrein ◽  
Early Disease ◽  
Kallikrein Activity

COVID-19 patients can present with pulmonary edema early in disease. We propose that this is due to a local vascular problem because of activation of bradykinin 1 receptor (B1R) and B2R on endothelial cells in the lungs. SARS-CoV-2 enters the cell via ACE2 that next to its role in RAAS is needed to inactivate des-Arg9 bradykinin, the potent ligand of the B1R. Without ACE2 acting as a guardian to inactivate the ligands of B1R, the lung environment is prone for local vascular leakage leading to angioedema. Here, we hypothesize that a kinin-dependent local lung angioedema via B1R and eventually B2R is an important feature of COVID-19. We propose that blocking the B2R and inhibiting plasma kallikrein activity might have an ameliorating effect on early disease caused by COVID-19 and might prevent acute respiratory distress syndrome (ARDS). In addition, this pathway might indirectly be responsive to anti-inflammatory agents.

scholarly journals Sequelae of Acute Respiratory Distress Syndrome: Interest of Rehabilitation

2019 ◽  
Vol 2019 ◽  
pp. 1-5 ◽  
Author(s):  
Elise Godeau ◽  
David Debeaumont ◽  
Elise Artaud-Macari ◽  
Laurie Lagache ◽  
Gurvan Le Bouar ◽  
...  
Keyword(s):  
Physical Activity ◽  
Acute Respiratory Distress Syndrome ◽  
Intensive Care ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Regular Physical Activity ◽  
Exertional Dyspnea ◽  
History Of ◽  
Alveolar Capillary

Case Presentation. This clinical case presents the history of a woman hospitalized for acute respiratory distress syndrome (ARDS). A 62-year-old woman, with regular physical activity and no history of respiratory disease or smoking, was hospitalized for moderate ARDS with bilateral pneumonitis. Fourteen days later, she was discharged from the intensive care unit and received respiratory physical therapy. One month later, she experienced exertional dyspnea. A regression of alveolar condensation with persistent sequelae at the pulmonary bases was noted. Three months later, the patient continued daily physical activity with satisfactory tolerance. A reduction in alveolar-capillary transfer, inappropriate hyperventilation upon exercise, and impairment of gas exchanges at maximal effort, suggestive of pulmonary shunt, were demonstrated. At the 6-month evaluation, the patient displayed exertional dyspnea with residual bilateral basal consolidations. Six months later, the dyspnea had ceased. The persistence of bilateral basal interstitial syndrome associated with bronchial dilatation and pleural-based consolidations was noted, as well as a stable impaired alveolar-capillary diffusing capacity. Discussion. Upon discharge from intensive care, pulmonary follow-up should be proposed to ARDS survivors. Moreover, pulmonary function testing at rest and exercise is advised as soon as possible to evaluate the respiratory sequelae. This will help to limit the severity of complications through adapted exercise rehabilitation and then regular physical activity.

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