Oxygen sensor of the heart

Abstract

How oxygen is sensed by the heart and what mechanisms mediate its sensing remain poorly understood. As recent reports show that low PO2 levels are detected by the cardiomyocytes in a few seconds, the rapid and short applications of low levels of oxygen (acute hypoxia), which avoid multiple effects of chronic hypoxia, may be used to probe the oxygen-sensing pathway of the heart. Here, we explored the oxygen-sensing pathway, focusing primarily on cellular surface membrane proteins that were first exposed to low PO2. Such studies suggest that acute hypoxia primarily targets the cardiac calcium channels, where either the channel itself or moieties closely associated with it, for instance heme-oxygenase-2 (HO-2) interacting through kinase phosphorylation, signal the α-subunit of the channel to the altered levels of PO2. Amino acids 1572–1651, the CaMKII phosphorylation sites (S1487 and S1545), CaM-binding sites (I1624 and Q1625), and Ser1928 of the carboxyl tail of the α-subunit appear to be critical residues that sense oxygen. Future studies on HO-2 knockout mice or CRISPR/Cas9 gene-edited human-induced pluripotent stem-cell-derived cardiomyocytes that reduce CaM-binding affinity are likely to provide deeper insights into the O2-sensing mechanisms.

Identification of Potential Targets of Stress Cardiomyopathy by a Machine Learning Algorithm

“…The results of GSVA may explain some of the clinical manifestations of stress cardiomyopathy (Figure 3D), such as the upregulation of the ESTROGEN RESPONSE EARLY function, thus suggesting that sex influences stress cardiomyopathy [24]. Interestingly, the upregulation of HEME METABOLISM and GLYCOLYSIS suggested that myocardial hypoxia and increased peripheral myocardium metabolism due to stress cardiomyopathy do indeed occur [29]. The upregulation of immune-related functions (IL2 STAT5 SIGNALING) and coagulation-related functions (COAGULATION) suggested that the belief that stress cardiomyopathy is self-limiting may be inaccurate.…”