Mechanistic insights into the cardiovascular effects of acute heat exposure: A multi-omics analysis based on a randomized crossover trial

Heat exposure has been identified as a significant contributory factor in the development of cardiovascular diseases, but the biological mechanisms are not yet fully elucidated. We conducted a randomized crossover trial in healthy adults in Shanghai, China. Each subject was alternatively exposed to moderate temperature (22 °C) and elevated temperature (32 °C) in a chamber for 2 h in random order. Blood pressure (BP) and arterial stiffness were measured before and after each exposure session. Genome-wide DNA methylation, untargeted serum proteomics, metabolomics, and 15 targeted serum biomarkers were analyzed. Linear mixed-effects models were used to analyze the data. The pathway enrichment was performed at the ingenuity pathway analysis platform. The network-based xMWAS analysis was further conducted. A total of 30 participants (15 males and 15 females) completed the trial, with an average age of 21.7 ± 1.5 years. Heat exposure was associated with higher pulse wave velocity (4.4 %, 95 % CI: 0.2, 6.8), augmentation index normalized to 75 bpm heart rate (190.7 %, 95 % CI: 19.0, 362.3) and reflection magnitude (35.9 %, 95 % CI: 12.3, 59.5). Exposure to heat was significantly associated with changes in 2 biomarkers on systemic inflammation, 2 on oxidative stress, 1 on coagulation, 2 on lipid metabolism, and 2 on atherosclerotic alterations. Multi-omics analyses indicated heat-induced perturbations in pathways were mostly related to systemic inflammation, oxidative stress, coagulation, and lipid metabolism disorder. Acute heat exposure might impair cardiovascular function and promote multiple adverse biological processes, especially those related to atherosclerosis progression and increase of plaque instability.