Πέμπτη 18 Μαΐου 2017

Regulation of Erythropoiesis after Normoxic Return from Chronic Sustained and Intermittent Hypoxia.

Hypoxia increases erythropoiesis mediated by hypoxia-inducible transcription factors (HIF) which regulate erythropoietin (EPO) transcription. Neocytolysis is a physiological mechanism that corrects polycythemia from chronic sustained hypoxemia (CSH) by transient, preferential destruction of young RBCs after normoxia is restored. We showed that neocytolysis is caused by excessive mitochondrial-derived reactive oxygen species (ROS) in reticulocytes mediated by down-regulation of HIF-controlled BNIP3L regulated mitophagy and a decrease in RBC antioxidant catalase (CAT) in hypoxia-produced erythrocytes. Decreased CAT results from hypoxia-induced miR-21 that downregulates CAT. This correlates with a transient acute decrease of HIF-1 at normoxic return that is associated with normalization of red cell mass. Obstructive sleep apnea (OSA), characterized by a unique pattern of chronic intermittent hypoxia (CIH), is associated with cardiovascular, endocrine and neurocognitive comorbidities, and increased cancer risk. The role of the carotid body in OSA modulated pathophysiologies has been well-studied; here we define hematological abnormalities and discuss the possible role of OSA blood changes on health. We found that only ~1% of OSA patients developed polycythemia, which was not attributable to other causes and corrected with continuous positive airway pressure therapy (CPAP) therapy. However, in our pilot OSA studies, we found increased ROS and mitochondrial mass with decreased CAT and BNIP3L in blood cells, along with increased inflammatory markers. After correction of OSA with use of CPAP for >3 months, some, but not all of these abnormalities corrected. The observed blood changes in OSA likely contribute to impaired health; however, their pathophysiological roles need to be carefully defined.



from Physiology via xlomafota13 on Inoreader http://ift.tt/2q2fODe
via IFTTT

Δεν υπάρχουν σχόλια:

Δημοσίευση σχολίου

Σημείωση: Μόνο ένα μέλος αυτού του ιστολογίου μπορεί να αναρτήσει σχόλιο.