Molecular Mechanisms of Vascular Damage During Lung Injury.
Adv Exp Med Biol
; 1304: 95-107, 2021.
Article
in English
| MEDLINE | ID: covidwho-1237449
ABSTRACT
A variety of pulmonary and systemic insults promote an inflammatory response causing increased vascular permeability, leading to the development of acute lung injury (ALI), a condition necessitating hospitalization and intensive care, or the more severe acute respiratory distress syndrome (ARDS), a disease with a high mortality rate. Further, COVID-19 pandemic-associated ARDS is now a major cause of mortality worldwide. The pathogenesis of ALI is explained by injury to both the vascular endothelium and the alveolar epithelium. The disruption of the lung endothelial and epithelial barriers occurs in response to both systemic and local production of pro-inflammatory cytokines. Studies that evaluate the association of genetic polymorphisms with disease risk did not yield many potential therapeutic targets to treat and revert lung injury. This failure is probably due in part to the phenotypic complexity of ALI/ARDS, and genetic predisposition may be obscured by the multiple environmental and behavioral risk factors. In the last decade, new research has uncovered novel epigenetic mechanisms that control ALI/ARDS pathogenesis, including histone modifications and DNA methylation. Enzyme inhibitors such as DNMTi and HDACi may offer new alternative strategies to prevent or reverse the vascular damage that occurs during lung injury. This review will focus on the latest findings on the molecular mechanisms of vascular damage in ALI/ARDS, the genetic factors that might contribute to the susceptibility for developing this disease, and the epigenetic changes observed in humans, as well as in experimental models of ALI/ADRS.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Respiratory Distress Syndrome
/
Acute Lung Injury
/
COVID-19
Type of study:
Experimental Studies
/
Prognostic study
Limits:
Humans
Language:
English
Journal:
Adv Exp Med Biol
Year:
2021
Document Type:
Article
Affiliation country:
978-3-030-68748-9_6
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