Abstract
Hypoxia-related microRNAs (miRNAs) are involved in the pathogenesis of various diseases. Because potential variations in miRNA expression mediated by hypoxic lung injury at high altitude remain incompletely characterized, we used a rat model to investigate the biochemical and miRNA changes induced by high-altitude hypoxia. After 24, 48, or 72 h of hypoxic exposure, expression of VEGF/Notch pathway-related proteins were increased in rat lung tissues. Microarray screening of hypoxic lung samples revealed 57 differentially expressed miRNAs, 19 of which were related to the VEGF/Notch signaling pathway. We verified that the top downregulated miRNA (miR-203a-3p) suppresses VEGF-A translation through direct binding and also indirectly reduces Notch1, VEGFR2, and Hes1 levels, which restricts the angiogenic capacity of pulmonary microvascular endothelial cells in vitro. These findings may aid in the development of new therapeutic strategies for the prevention and treatment of hypoxic lung injury at high altitude.
Highlights
Hypoxia is the most critical cause of acute mountain sickness (AMS) [1, 2]
In the hypoxiaexposed groups the intrapulmonary structure was damaged, red blood cells were visible in the alveoli and pulmonary septum, and pink fluid exudate was found in the alveoli
TCO2, HCO3 and base excess extracellular fluid (BEecf) were all markedly reduced after 72-h hypoxia, compared with the values recorded at shorter treatment times (Figure1B)
Summary
At high-altitude environments (above 2,500 meters) air oxygen levels remain constant, but as the altitude increases the oxygen partial pressure (PaO2) drops [3, 4]. In non-acclimatized individuals, this reduction in PaO2 can cause arterial desaturation or hypoxemia, which restricts the diffusion of oxygen into alveolar capillaries and lung tissue and may lead to lifethreatening conditions, i.e. high-altitude pulmonary edema (HAPE) and high-altitude cerebral edema (HACE) [3, 5]. Research showed that in high-altitude environments, hypoxia is the main stimulating factor of angiogenesis, a physiological response to oxygen deprivation [6]. The regulation of the VEGF/Notch pathway and its impact on angiogenic events related to hypoxic lung injury at high-altitude are not fully understood
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
