This report describes a Drosophila system for assessing response and recovery of the heart in conditions of hypoxia. Responses of wild-type flies and flies carrying a mutation in the sima gene have been compared. Dmel\sima encodes a transcription factor that plays a key role in the cellular response to hypoxia in flies. There are several genes orthologous to sima in human: HIF1A, EPAS1 (also known as HIF2A), and HIF3A. Heart physiology and function in hypoxia-selected flies, selected over many generations for survival in a low-oxygen environment, have also been characterized.
UAS constructs of the wild-type human Hsap\HIF1A gene have been introduced into flies, but have not been characterized in the context of this disease model.
Cardiac responses to acute (30 min), sustained (18 h), and chronic (3 wk) hypoxia with reoxygenation were assessed in wild-type flies and flies homozygous for a loss-of-function allele of sima. Hearts from wild-type flies recovered quickly after acute hypoxia, however, exposure to sustained or chronic hypoxia significantly compromised heart function upon reoxygenation. Hearts from flies carrying a sima loss-of-function allele exhibited exaggerated reductions in cardiac output in response to hypoxia.
[updated Feb. 2020 by FlyBase; FBrf0222196]
In human, hypoxia inducible factors HIF1A and HIF2A belong to a group of transcription factors which mediate most of the cellular responses to hypoxia at a transcriptional level, in tissues throughout the body (Abe et al., 2017; pubmed:28757538).
In the human heart, gene expression is adjusted to oxygen availability by several mechanisms, including regulation of gene transcription by the hypoxia-inducible basic helix-loop-helix transcription factor HIF1A (Giordano, 2005; pubmed:15765131).
Moderate-scoring ortholog of human HIF1A, HIF3A, and EPAS1 (1 Drosophila to 3 human). Dmel\sima shares 28-29% identity and 44-47% similarity with the human genes.
