Cardiac Adaptation For Chronic Hypoxia

1153 WordsAug 22, 20165 Pages
The stabilised HIF-1α translocates to the cell nucleus from the cytoplasm and dimerise with ARNT to form the HIF-1 heterodimer. The abundance of the HIF-1 transcription factor in the nucleus alters the affinity of the promoter region by binding to the RNA polymerase II. The formation of the HIF-1 activates the promoter region of its target genes (figure 3), inducing their expression (Chilov et al., 1999) that results in greater glucose uptake and lactate efflux, reduction in mitochondrial respiration and increased blood flow through the vessels, which augments oxygen and energy delivery to the heart and maintaining cardiac function. These observations demonstrate that the constitutively expressed ARNT and HIF-1α accumulation are the prerequisites to HIF-1 mRNA expression, confirming that activation of HIF-1 primarily depends on hypoxia-induced stabilisation of HIF-1α and ARNT, which is otherwise rapidly degraded in oxygenated cells (figure 1) (Lange et al., 2011). 2.1.2. Cardiac adaptation to hypoxia Cardiac adaptation to chronic hypoxia is characterised by a variety of functional changes to maintain homeostasis with minimum energy expenditure. Such adjustments are to enable protection of the cardiac system under conditions when the workload is increased and eventually the upregulation of hypoxia-sensitive genes in glucose metabolism and increased lactate production, n consistent with an anaerobic pattern of metabolism (Malhotra et al., 1999; Silverman et al.,

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