Perwez Alam, Neeru Saini, M A Qadar Pasha1. 1. CSIR-Institute of Genomics and Integrative Biology, Mall Road, Delhi-110 007, India. qpasha@igib.res.in.
Abstract
BACKGROUND: High-altitude (HA) attracts people for its beauty and adventure. Interestingly, however, it affects the normal physiology and health due to the hypobaric hypoxic environment. Normal individuals acclimatize efficiently, but susceptible individuals encounter HA related disorders. Among these disorders, high-altitude pulmonary edema (HAPE) results into casualties. During acclimatization, body makes sequential changes in the expression of genes to counterbalance the hypobaric hypoxia induced stress. In this context, gene regulatory elements, such as transcription factors, DNA methylation and microRNAs (miRNAs) become relevant. This review, however, will primarily focus on miRNAs because of its decisive role in maintaining physiological homeostasis, both under normoxic and hypoxic conditions. METHODS: Availing the literature, an in-silico study was performed to explore the anticipated role of miRNAs in HAPE pathophysiology. RESULTS: We observed robust target based networking among the miRNAs. miR-16, 20b, 22, 206 and 17/92 were reported to have decreased expression in response to hypoxia and inhibit ion channels and increase pulmonary arterial pressure leading to vascular dysfunction and loss of cellular integrity. Whereas, miR-23b, 26a and 155 inhibit TGF signaling and contribute to increased pulmonary pressure, while miR-210 inhibits mitochondrial function. Incidentally, these physiological func- tions associate with HAPE, favoring possible role of miRNAs. CONCLUSION: It is concluded that the expression of individual/groups of miRNAs may change differentially under hypobaric hypoxia to modulate human physiology; however, this needs to be validated for HAPE pathophysiology.
BACKGROUND: High-altitude (HA) attracts people for its beauty and adventure. Interestingly, however, it affects the normal physiology and health due to the hypobaric hypoxic environment. Normal individuals acclimatize efficiently, but susceptible individuals encounter HA related disorders. Among these disorders, high-altitude pulmonary edema (HAPE) results into casualties. During acclimatization, body makes sequential changes in the expression of genes to counterbalance the hypobaric hypoxia induced stress. In this context, gene regulatory elements, such as transcription factors, DNA methylation and microRNAs (miRNAs) become relevant. This review, however, will primarily focus on miRNAs because of its decisive role in maintaining physiological homeostasis, both under normoxic and hypoxic conditions. METHODS: Availing the literature, an in-silico study was performed to explore the anticipated role of miRNAs in HAPE pathophysiology. RESULTS: We observed robust target based networking among the miRNAs. miR-16, 20b, 22, 206 and 17/92 were reported to have decreased expression in response to hypoxia and inhibit ion channels and increase pulmonary arterial pressure leading to vascular dysfunction and loss of cellular integrity. Whereas, miR-23b, 26a and 155 inhibit TGF signaling and contribute to increased pulmonary pressure, while miR-210 inhibits mitochondrial function. Incidentally, these physiological func- tions associate with HAPE, favoring possible role of miRNAs. CONCLUSION: It is concluded that the expression of individual/groups of miRNAs may change differentially under hypobaric hypoxia to modulate human physiology; however, this needs to be validated for HAPE pathophysiology.