Passive heat therapy protects against endothelial cell hypoxia‐reoxygenation via effects of elevations in temperature and circulating factors

Abstract

Repeated exposure to passive heat stress ('heat therapy') has widespread physiological benefits, including cellular protection against novel stressors. Increased heat shock protein (HSP) expression and upregulation of circulating factors may impart this protection. We tested the isolated abilities of mild heat pretreatment and serum from human subjects (n = 10) who had undergone 8 weeks of heat therapy to protect against cellular stress following hypoxia-reoxygenation (H/R), a model of ischaemic cardiovascular events. Cultured human umbilical vein endothelial cells were incubated for 24 h at 37°C (control), 39°C (heat pretreatment) or 37°C with 10% serum collected before and after 8 weeks of passive heat therapy (four to five times per week to increase rectal temperature to ≥ 38.5°C for 60 min). Cells were then collected before and after incubation at 1% O for 16 h (hypoxia; 37°C), followed by 20% O for 4 h (reoxygenation; 37°C) and assessed for markers of cell stress. In control cells, H/R increased nuclear NF-κB p65 protein (i.e. activation) by 106 ± 38%, increased IL-6 release by 37 ± 8% and increased superoxide production by 272 ± 45%. Both heat pretreatment and exposure to heat therapy serum prevented H/R-induced NF-κB activation and attenuated superoxide production; by contrast, only exposure to serum attenuated IL-6 release. H/R also decreased cytoplasmic haemeoxygenase-1 (HO-1) protein (known to suppress NF-κB), in control cells (-25 ± 8%), whereas HO-1 protein increased following H/R in cells pretreated with heat or serum-exposed, providing a possible mechanism of protection against H/R. These data indicate heat therapy is capable of imparting resistance against inflammatory and oxidative stress via direct heat and humoral factors.

Passive heat therapy for cerebral protection: new ideas of age‐old concepts

“…() sought to identify the potential mechanisms underlying the physiological benefits of passive heat therapy, specifically for protection against cellular stress. By developing an in vitro model of hypoxia–reoxygenation, Brunt and colleagues isolated the effects of heat stress and the influence of circulating factors on endothelial cell protection. Simply heating endothelial cells mitigated the inflammatory and oxidative stress response to hypoxia–reoxygenation.…”

“…This raises the question of whether the cellular protection observed by Brunt et al . manifests in neurons or cerebral microvascular endothelial cells. An intriguing avenue of research may be emerging from perennial cultural practices.…”

“…Of course, the epidemiological nature of this study does not provide a physiological explanation but, importantly, the observations were adjusted for health risk factors, lifestyle and socioeconomic status. Whether heat therapy promotes a resilient brain in humans merits investigation, and the recent data reported by Brunt et al . provide an intriguing hypothesis regarding a potential mechanism to explain the association between sauna bathing and the risk of Alzheimer's disease and cognitive decline (Laukkanen et al . ).…”

“…These studies provide evidence to support the hypothesis that, broadly similarly to Brunt et al . (), both acute and chronic heat treatment induce beneficial cellular responses and afford at least some level of protection against cellular stress. However, the effects of heat therapy for cerebral protection in humans and its potential mechanisms (e.g.…”

“…Collectively, these data warrant further investigation of heat acclimation, HSP expression, and their effects on the human cerebral circulation. Regardless, isolating temperature from circulating factors and shear‐mediated mechanisms in humans is difficult, if not impossible, and Brunt et al . are therefore commended for their study combining in vitro models with human serum to provide insight on the mechanisms involved in heat therapy.…”