The Effect of Waon Therapy on Failed Myocardium and Ischemic Limb via Heat Shock Proteins / 日本温泉気候物理医学会雑誌

ABSTRACT

 Waon therapy uses a far infrared-ray dry sauna, which is evenly maintained at 60°C and differs from the traditional sauna. The patients were placed in a 60°C sauna system for 15 minutes, in which the deep-body temperature has increased by 1.0 to 1.2°C. Then, after leaving the sauna, they underwent bed rest with a blanket to keep them warm for an additional 30 minutes. All patients were weighed before and after the therapy, and they drank some water at the end of Waon therapy to compensate for weight lost due to perspiration and prevent the dehydration.  We have previously reported that Waon therapy improves the cardiac and vascular endothelial function in patients with chronic heart failure (CHF) and the limb ischemia and symptoms in patients with arteriosclerosis obliterans (ASO). As underlying molecular mechanisms, we demonstrated that Waon therapy upregulates nitric oxide (NO) and endothelial NO synthase (eNOS), which would improve vascular endothelial and cardiac function in TO-2 cardiomyopathic hamsters and augment ischemia-induced angiogenesis. In order to investigate the mechanism of Waon therapy, we examined the effect of Waon therapy on heat shock proteins (Hsp) in failed myocardium and ischemic limb. Hsp are stress response proteins that can be induced by stress signals, including thermal stimulation. Hsp function as chaperones to assist with protein folding in order to protect cells from protein denaturation or cell death under stress conditions.  In TO-2 cardiomyopathic hamsters, the cardiac expression of 4-hydroxy-2-nonenal (4HNE), a marker of oxidative stress, was decreased in the 4-week Waon therapy compared to untreated hamsters. Also, the cardiac expressions of Hsp 27, Hsp 32 and manganese superoxide dismutase (Mn-SOD), which reduce oxidative stress, were significantly upregulated by the 4-week Waon therapy compared to untreated hamsters. In addition, Waon therapy upregulated Hsp90, which contributes to the activation of the AkteNOSNO pathway, and induced angiogenesis in mice with hindlimb ischemia. However, Waon therapy did not increase the expression of Hsp70, Hsp60, Hsp32 and Hsp27 in the same model mice. The thermal stimulation with Waon therapy upregulated specific Hsp isoforms depending on different organs and diseases. The specific function of Hsp induced by Waon therapy is suggested to play an important role in improving cardiovascular diseases.