Research Progress in the Role of Hypoxia-Inducible Factor 1 in Altitude Sickness and the Mechanisms Involved
Individuals who reside at high altitudes for extended periods or those who visit these regions briefly frequently experience high-altitude response,which triggers a series of physiological and pathological changes in the body,ultimately causing altitude sickness.One of the most critical features of high-altitude environments is hypoxia.Recent studies have demonstrated that hypoxia-inducible factor 1(HIF-1)plays a central role in mediating the body's response to hypoxic conditions at high altitudes.HIF-1,a heterodimeric transcription factor composed of an oxygen-sensitive subunit α(HIF-1α)and a constitutively expressed subunit β(HIF-1β),directly regulates the expression of multiple target genes,thereby modulating various physiological processes essential for cellular adaptation to hypoxia.According to a substantial body of research,aberrant expression of HIF-1 is implicated in the pathogenesis and progression of various diseases,including altitude sickness,cardiovascular disorders,neurological conditions,inflammatory diseases,cognitive impairment,immune dysregulation,and cancer.In this review,we provided an in-depth examination of the structural characteristics and regulatory mechanisms governing HIF-1 expression,discussed its downstream target genes,and highlighted the inhibitors currently under development.Additionally,we summarized the pivotal role and underlying mechanisms of HIF-1 in the development of altitude sickness,particularly its regulatory role in the pathophysiological processes of high-altitude pulmonary edema(HAPE),high-altitude cerebral edema(HACE),and high-altitude pulmonary hypertension(HAPH).Through a thorough examination of the role of HIF-1,we aim to provide a theoretical foundation and potential therapeutic targets for the prevention and treatment of altitude sickness.
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