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

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 degrees C (control), 39 degrees C (heat pretreatment) or 37 degrees 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 degrees C for 60 min). Cells were then collected before and after incubation at 1% O-2 for 16 h (hypoxia; 37 degrees C), followed by 20% O-2 for 4 h (reoxygenation; 37 degrees C) and assessed for markers of cell stress. In control cells, H/R increased nuclear NF-kappa B 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-kappa B 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-kappa B), 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.