Cardiac Adaptation For Chronic Hypoxia

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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…show more content…
In this case, cardiac adaptation offers the cardiac protection to all the major deleterious consequences of acute oxygen deficiency. Furthermore, other adaptive responses to chronic hypoxic adaptations include hypertrophy of the right ventricle and hypoxic pulmonary hypertension as a result of pressure-overload and vasoconstriction that could lead to congestive heart failure during severe hypoxia (Sano et al., 2007). Since fetal environment corresponds to ~8000m altitude, prenatal defense to hypoxia consists of a long-term adaptation to limited intrauterine oxygen supply (Singer, 1999). Hence, the immature heart is more resistant to hypoxia as opposed to the adult myocardium, which may explain the significantly lower MI incidences during early ontogenetic development. In adults, cardiomyocytes are particularly susceptible to low oxygen supply and consequently hypoxia-induced cell death, whereas fetal cardiomyocytes are much more adapted (Breckenridge et al., 2013). Of all the stress that the fetus encounters, hypoxia may be the most common that affect the homeostasis of an organism, and perhaps the most clinically relevant (Malhotra et al., 1999). 2.1.3. ARNT in cardiovascular diseases Chronic exposure of mice to hypoxia induces a major remodelling of the vasculature. The right ventricle of the heart undergoes hypertrophy, pulmonary arteries thickened as a result of increased right ventricular pressure, reduced lumen diameter and increased blood
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