American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Feb 2023
Obstructive Sleep Apnea-induced Endothelial Dysfunction is Mediated by miR-210.
Rationale: Obstructive sleep apnea (OSA)-induced endothelial cell (EC) dysfunction contributes to OSA-related cardiovascular sequelae. The mechanistic basis of endothelial impairment by OSA is unclear. Objectives: The goals of this study were to identify the mechanism of OSA-induced EC dysfunction and explore the potential therapies for OSA-accelerated cardiovascular disease. ⋯ Mechanistically, intermittent hypoxia-induced SREBP2 (sterol regulatory element-binding protein 2) bound to the promoter region of miR-210, which in turn inhibited the iron-sulfur cluster assembly enzyme and led to mitochondrial dysfunction. Moreover, the SREBP2 inhibitor betulin alleviated intermittent hypoxia-increased systolic blood pressure in the OSA mouse model. Conclusions: These results identify an axis involving SREBP2, miR-210, and mitochondrial dysfunction, representing a new mechanistic link between OSA and EC dysfunction that may have important implications for treating and preventing OSA-related cardiovascular sequelae.
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Am. J. Respir. Crit. Care Med. · Feb 2023
Rethinking ARDS After COVID-19. If a "Better" Definition is the Answer, What is the Question?
The definition of acute respiratory distress syndrome (ARDS) has a somewhat controversial history, with some even questioning the need for the term "ARDS." This controversy has been amplified by the coronavirus disease (COVID-19) pandemic given the marked increase in the incidence of ARDS, the relatively new treatment modalities that do not fit neatly with the Berlin definition, and the difficulty of making the diagnosis in resource-limited settings. We propose that attempts to revise the definition of ARDS should apply the framework originally developed by psychologists and social scientists and used by other medical disciplines to generate and assess definitions of clinical syndromes that do not have gold standards. ⋯ Future revisions of the definition of ARDS should contain the purpose, the methodology, and the framework for empirically testing any proposed definition. Attempts to revise critical illness syndromes' definitions usually hope to make them "better"; our recommendation is that future attempts use the same criteria used by other fields in defining what "better" means.