Age-Dependent Changes in the Pulmonary Renin-Angiotensin System Are Associated With Severity of Lung Injury in a Model of Acute Lung Injury in Rats

Schouten, Laura R. A.; Helmerhorst, Hendrik J. F.; Wagenaar, Gerry T. M.; Haltenhof, Tom; Lutter, René; Roelofs, Joris J. T. H.; Woensel, Job B. M. van; Kaam, A.H.L.C. van; Bos, Albert P.; Schultz, Marcus J.; Walther, Thomas; Asperen, Roelie M. Wösten–van

doi:10.1097/ccm.0000000000002008

Cited by 52 publications

(40 citation statements)

References 37 publications

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“…28 In one study about the pathophysiology of acute respiratory distress syndrome (ARDS), increasing age led to an imbalance of the pulmonary renin-angiotensin system, which correlates with aggravated inflammation and enhanced lung injury in a rat model. 29 Nevertheless, no age-dependent differences in ACE and ACE2 were seen in a prospective observational cohort study. 30 There is one hypothesis that smoking increases ACE2 expression and thus enhances coronavirus entry into pulmonary epithelial cells.…”

Section: Discussionmentioning

confidence: 92%

Clinical characteristics and diagnostic challenges of pediatric COVID-19: A systematic review and meta-analysis

Chang

2020

Journal of the Formosan Medical Association

216

247

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Section: Discussionmentioning

confidence: 92%

Clinical characteristics and diagnostic challenges of pediatric COVID-19: A systematic review and meta-analysis

Chang

2020

Journal of the Formosan Medical Association

216

247

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“…Both AT1R blocker (ARB) and exogenous supplementation of rhuACE2 significantly ameliorated ALI, improved lung function and survival rate of mice 41‐43 . Last but not least, in an ALI model of rat, aged subjects showed significantly decreased ratio of ACE2/ACE in their bronchoalveolar lavage fluid, which aggravated their ALI, 38,44 suggesting that age‐dependent changes in the pulmonary RAS were associated with severity of lung injury. Therefore, maintaining the balance between ACE2 and ACE is very important.…”

Section: Ace2 Protects Body In Multiple Pathological Scenarios Includmentioning

confidence: 99%

Angiotensin‐converting enzyme 2 in severe acute respiratory syndrome coronavirus and SARS‐CoV‐2: A double‐edged sword?

Yan¹,

Xiao²,

Lin³

2020

FASEB j.

105

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Human angiotensin‐converting enzyme 2 (ACE2) facilitates cellular entry of severe acute respiratory syndrome coronavirus (SARS‐CoV) and SARS‐CoV‐2 as their common receptor. During infection, ACE2‐expressing tissues become direct targets, resulting in serious pathological changes and progressive multiple organ failure or even death in severe cases. However, as an essential component of renin‐angiotensin system (RAS), ACE2 confers protective effects in physiological circumstance, including maintaining cardiovascular homeostasis, fluid, and electrolyte balance. The absence of protective role of ACE2 leads to dysregulated RAS and thus acute changes under multiple pathological scenarios including SARS. This potentially shared mechanism may also be the molecular explanation for pathogenesis driven by SARS‐CoV‐2. We reasonably speculate several potential directions of clinical management including host‐directed therapies aiming to restore dysregulated RAS caused by ACE2 deficiency. Enriched knowledge of ACE2 learned from SARS and COVID‐19 outbreaks can provide, despite their inherent tragedy, informative clues for emerging pandemic preparedness.

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“…Besides, most experiments use young male rodents that almost never have comorbidities for the evaluation of new treatments for ARDS, while patient populations seen in intensive care units are elderly and frequently have concomitant diseases such as diabetes mellitus, chronic obstructive pulmonary disease or active cancer [54]. The few studies that compared elderly rodents to younger ones indeed found a difference in the biological response between these groups [55,56].…”

Section: Ineffective Interventionsmentioning

confidence: 99%

ARDS: challenges in patient care and frontiers in research

2018

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This review discusses the clinical challenges associated with ventilatory support and pharmacological interventions in patients with acute respiratory distress syndrome (ARDS). In addition, it discusses current scientific challenges facing researchers when planning and performing trials of ventilatory support or pharmacological interventions in these patients.Noninvasive mechanical ventilation is used in some patients with ARDS. When intubated and mechanically ventilated, ARDS patients should be ventilated with low tidal volumes. A plateau pressure <30 cmH 2 O is recommended in all patients. It is suggested that a plateau pressure <15 cmH 2 O should be considered safe. Patient with moderate and severe ARDS should receive higher levels of positive endexpiratory pressure (PEEP). Rescue therapies include prone position and neuromuscular blocking agents. Extracorporeal support for decapneisation and oxygenation should only be considered when lungprotective ventilation is no longer possible, or in cases of refractory hypoxaemia, respectively. Tracheotomy is only recommended when prolonged mechanical ventilation is expected.Of all tested pharmacological interventions for ARDS, only treatment with steroids is considered to have benefit.Proper identification of phenotypes, known to respond differently to specific interventions, is increasingly considered important for clinical trials of interventions for ARDS. Such phenotypes could be defined based on clinical parameters, such as the arterial oxygen tension/inspiratory oxygen fraction ratio, but biological marker profiles could be more promising.

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Age-Dependent Changes in the Pulmonary Renin-Angiotensin System Are Associated With Severity of Lung Injury in a Model of Acute Lung Injury in Rats

Cited by 52 publications

References 37 publications

Clinical characteristics and diagnostic challenges of pediatric COVID-19: A systematic review and meta-analysis

Clinical characteristics and diagnostic challenges of pediatric COVID-19: A systematic review and meta-analysis

Angiotensin‐converting enzyme 2 in severe acute respiratory syndrome coronavirus and SARS‐CoV‐2: A double‐edged sword?

ARDS: challenges in patient care and frontiers in research

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