Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004135 (ATM)
 13,001 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Morbidity and mortality rates of ARDS (acute respiratory distress syndrome) are high in patients with a history of chronic alcohol abuse. In addition to susceptibility to lung infection, alteration of local cellular functions in the lung has recently been proposed as a new mechanism of exacerbation of ARDS in patients with a history of chronic alcohol abuse. Clinical studies and studies using animal experiments have shown that a decrease in lung glutathione levels is associated with exacerbation of ARDS in chronic alcohol abuse. In the alcoholic lung, depletion of glutathione increases oxidative stress derived from activated neutrophils, resulting in decreased surfactant production, apoptosis and increased permeability of alveolar epithelial type II cells, in which TGF-beta1 may be involved. Acetoaldehyde has been suggested to be involved in the mechanism of exacerbation of ARDS by inducing lung remodeling through stimulation of fibronectin expression following nicotinic acetylcholine receptor stimulation and CREB activation in chronic alcohol abuse. More recently, antagonists of angiotensin II type-1 receptor (AT1 receptor) have been shown to prevent glutathione depletion, increase in TGF-beta1 expression and lung edema in endotoxemic rats with chronic alcohol administration. On the other hand, macrophage-derived prostaglandin E2 plays a protective role at an initial phase of ARDS by inhibiting cytokine production by macrophages and extravascular invasion of activated neutrophils. Our recent studies have shown that LPS-induced COX-2 expression and subsequent prostaglandin E2 production in rat alveolar macrophages are inhibited by ethanol incubation in vitro and ethanol administration in vivo. Only a decade has passed since alcohol abuse was demonstrated to be associated with increased mortality of ARDS and future studies are needed to clarify the mechanism underlying alcohol-induced exacerbation of ARDS.
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PMID:[Alcohol abuse as a risk factor for ARDS]. 1717 45

: ACE2 receptor has a broad expression pattern in the cellular membrane and provides a protective action against the development of cardiovascular diseases. Recently, this enzyme has become of extreme interest during the pandemic infection of COVID-19 (coronavirus disease 2019). This virus invades alveolar epithelium and cardiomyocytes using ACE2 as a transmembrane receptor. ACE2 is a counter-regulatory peptide that degrades Ang II into Ang 1-7, thereby attenuating the biological effects of the AT1 receptor. The binding between the spike protein of COVID-19 and the enzyme is crucial for the virus to enter the target cells, but whether an increase in ACE2 activity could facilitate the infection is not yet demonstrated. However, this aspect has raised many concerns about the use of ACE inhibitors or ARBs in infected patients or patients at risk of infection. It appears that cellular infection leads to a reduction in ACE2 expression and an increase in the activity of the Ang II--AT1 axis, which leads to the release of pro-inflammatory cytokines, ARDS, myocarditis, and hypercoagulability with the possibility of exacerbation of acute coronary syndrome, induction of pulmonary embolism, or appearance of disseminated intravascular coagulation. Therefore, ACE inhibitors or angiotensin receptor blocker drugs should be continued in infected patients, as their discontinuation can increase Ang II activity and induce injury to the lungs or cardiovascular system.
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PMID:Focus on clinical practice: angiotensin-converting enzyme 2 and corona virus disease 2019: pathophysiology and clinical implications. 3274 Apr 95