The Effects of Passive Heat Stress on Serum microRNA Expression in Young Healthy Adults

Introduction: The physiological and cellular responses to acute heat stress in humans are well characterised, however the response of microRNA (miRNA) has not yet been established. We investigated the effects of acute passive heat stress on the expression of serum miRNA to further characterise the human molecular response to heat stress in young healthy adults. We hypothesised that prolonged, passive heat stress would induce detectable changes in miRNA in human serum and that the miRNAs would be differentially expressed at both +0.6°C and +1.2°C above baseline core temperature. Methods: 8 participants (4F/4M, 23±3 y) were exposed to 50°C heat using a water perfused suit, in which 8mL blood was obtained at baseline (BL, T0), and when core temperature increased to +0.6°C (T1) and +1.2°C (T2) above BL. Serum was separated and stored for further analysis. miRNA isolation and library preparation were conducted, and samples were sequenced and analysed. Differentially expressed miRNAs were determined and downstream gene targets were predicted. Rectal temperature (Trec), skin temperature (Tsk), heart rate (HR), systolic (SBP) and diastolic blood pressure (DBP) were monitored continuously throughout the protocol and averaged over 60 s at T0, T1 and T2. Perceptions of thermal sensation (TS), thermal comfort (TC), and affect were obtained every 10 min. Results: Average time to reach T2 (Trec +1.2ºC above baseline) was 82±11 min. Average absolute Trec at T2 was 38.4±0.3ºC. Trec, Tsk and HR increased over the duration of the heat stress protocol and were significantly different between each timepoint (p<0.001). SBP and DBP remained stable and was not different between timepoints (P>0.05). Measures of TS, TC and affect resulted in participants feeling significantly hotter, more uncomfortable, and worse at T1 and T2 compared to T0 (p<0.001). 17 miRNAs were identified as differentially expressed in heat stress, with 13 upregulated and 4 downregulated at T2 compared to T0 (p<0.05). No significant differences in miRNA expression were observed between T1 and T0, or T1 and T2, nor between sexes (P>0.05). Exploratory analyses identified significant differences (p<0.05) between two distinct groups of “low” and “high” responders (n=4 per group) for end absolute Trec, average TS and average affect, however these differences were not associated with differential miRNA responses (P>0.05). Downstream signalling pathways associated with differentially expressed miRNAs included regulation of apoptosis, inflammatory responses, and heat stress responses. Conclusion: This study characterised the serum miRNA response to passive heat stress in humans, identifying at least 17 miRNAs that play a role when young, healthy humans are exposed to moderate levels of heat stress. Downstream signalling processes relating to heat stress were enriched, supporting the finding that these miRNAs may be responsible for regulatory mechanisms in the human heat-stress response. This project was supported by a small grant from the Institute of Climate, Energy and Disaster Solutions at the Australian National University. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.