Background Cardiovascular disease remains the leading cause of death in the United States, primarily due to the unsuccessful recovery of cardiac tissue from oxygen-deprived injuries. The severity of these insults varies among individuals and is often influenced by genetic factors. Despite extensive research, the specific genes involved in hypoxic response still remain unclear. Therefore, this study aims to characterize gene expression variability in response to the hypoxic event, since identifying these genetic markers will be crucial for early intervention in populations at high risk for oxygen-related cardiac complications.

Methods Hypoxic stress was induced on two genetically distinct mice strains: hypoxia-sensitive (CD1) and hypoxia-resistant (C57BL/6J). We then performed a microarray on cardiac tissue samples from these mice to quantify the expression patterns of coding and non-coding (lncRNAs) genes. Using correlational and enrichment analysis methods, we compared the differential gene expression patterns between the two mice strains. Previous studies have reported limited success in identifying hypoxia-associated genetic markers, thus justifying our study’s emphasis on non-coding RNA profiles.

Results Our data revealed that the most significant lncRNA differential expression patterns are involved in energy metabolism and conservation. This specifically included “protein secretion” and “oxidation-reduction processes” according to GeneOntology (GO) term descriptions. In the “regulation in protein secretion” GO Term, we discovered that the lncRNA XR_001783868.2 exhibited a 28% increase in expression in response to hypoxia. This lncRNA overlaps with the coding gene Fhip1a/FAM160A1 and may play a role in regulating its gene expression in response to hypoxia.

Conclusion lncRNAs associated with heightened sensitivity to hypoxia may serve as genetic markers for identifying individuals at increased risk of cardiovascular-related mortality, supporting the development of preventive and targeted treatment strategies.