2026, 6(2): 97-108.
doi: 10.1515/fzm-2026-0010
Objective Exposure to extreme cold temperatures may increase the risk of cardiovascular diseases. This study aimed to investigate the effects of cold exposure on the heart and its underlying mechanisms using an integrated transcriptomic and metabolomic approach. Methods C57BL/6 mice were subjected to cold exposure at 4 ℃ for 12 hours per day for 4 weeks. Transcriptomics and metabolomics profiles of the heart were analyzed. Differentially expressed genes (DEGs) and differentially expressed metabolites (DEMs) were identified, and mRNA expression levels were validated by qRT-PCR. Enrichment analyses were performed to identify significantly affected pathways. Transcriptomic and metabolomic data were then integrated to provide a comprehensive view of molecular alterations induced by cold exposure. To further evaluate the relationship between cold exposure and cardiovascular diseases, a myocardial infarction (MI) mouse model was established, and overlapping genes between cold exposure and MI were analyzed. Results Cold exposure significantly altered both the transcriptomic and metabolomic profiles of mouse hearts. Pathway enrichment analyses based on DEGs and DEMs identified several signaling pathways affected by cold stress. Integrated transcriptomic and metabolomic analyses further highlighted potential metabolic and signaling pathways associated with cold exposure. By cross-referencing DEGs associated with cold exposure with those from the MI model in the GEO database (GSE223208), 34 overlapping genes were identified. Integrated analyses implicated key genes (Tnfrsf12a and Nppb) in cold-aggravated cardiac remodeling, which were further validated in MI models. Conclusion Cold exposure reprograms the cardiac transcriptome and metabolome in mice. Cold exposure and MI share a subset of DEGs, which may help illuminate the pathophysiological interplay between cold stress and MI, highlighting potential therapeutic targets for cold-exacerbated cardiovascular diseases.
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