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n patients with chronic heart failure (CHF), vascular resistance is increased through the activation of neurohumoral systems, such as the sympathetic nervous, renin-angiotensin and endothelin systems. 1 Vascular endothelial function, which is mainly represented by endothelium-dependent vasodilatory function through the production of vasodilators derived from the endothelium such as nitric oxide (NO), prostacyclin and endothelium-derived hyperpolarizing factors, is impaired in CHF and affects clinical symptoms. 2-5 Impaired vascular endothelial function leads to increased vascular tone and vascular remodeling, which reduces peripheral blood flow and oxygen delivery to the skeletal muscles, followed by progressive exercise intolerance and clinical symptoms. [2][3][4][5] Therapies that improve endothelial function, such as angiotensin-converting enzyme inhibitors and regular exercise, improve the clinical symptoms and prognosis in CHF. [6][7][8][9] We reported that sauna therapy at 60°C induces vasodilation of the systemic and pulmonary arteries and veins, reduces cardiac preload and afterload and improves hemodynamics, clinical symptoms and cardiac arrythmia in patients with CHF. [10][11][12] We also clarified that the beneficial effects of sauna therapy for CHF are caused by improved vascular endothelial function and the normalizing of the neurohormonal systems. 13 Furthermore, we showed that repeated sauna therapy improved the survival of cardiomyopathic hamsters with CHF. 14 Vascular endothelial dysfunction in CHF is mainly due to decreased NO production induced by decreased levels of endothelial NO synthase (eNOS) expression and increased oxidative stress. [15][16][17] We have already reported that repeated sauna therapy increased arterial eNOS protein and mRNA expressions from the normal levels in healthy hamsters. 18 However, it is important to determine whether repeated sauna therapy could increase eNOS expression downregulated by CHF. The present study aims to investigate whether repeated sauna therapy modulates eNOS expression and NO production in CHF. Methods AnimalsWe used male TO-2 cardiomyopathic hamsters (Bio Breeders, Fitchburg, MA, USA) as a model of clinical dilated cardiomyopathy. These animals develop CHF (characterized by symptoms such as general edema and pleural effusion) at around 30 weeks of age and die within a year. 19,20 Male Syrian golden hamsters (Japan SLC, Hamamatsu, Japan) served as normal controls. All animals Background Vascular endothelial dysfunction is involved in the pathophysiology of chronic heart failure (CHF). It has been reported that sauna therapy, which allows thermal vasodilation, improves vascular endothelial dysfunction in patients with CHF. The present study investigates the mechanisms through which sauna therapy improves endothelial dysfunction induced by CHF. Methods and ResultsNormal control and male TO-2 cardiomyopathic hamsters were used. Thirty-week-old TO-2 hamsters were treated daily with an experimental far infrared-ray dry sauna system for 15 min at 39°C f...

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Background-Understanding the precise molecular mechanisms underlying the phenomenon of restenosis after PTCA may help us to develop a new strategy for the treatment of restenosis after PTCA. The purpose of this study was to identify the genes involved in vascular restenosis. Methods and Results-Applying a differential hybridization method to a model of the balloon-injured rabbit aorta, we identified 6 cDNA clones that were upregulated after injury. Northern blot showed that 5 genes, but not apolipoprotein J (apoJ)/clusterin, were constitutively expressed in noninjured aorta and upregulated after balloon injury. ApoJ mRNA was not detectable in noninjured aorta (control), began to be expressed at 6 hours after injury, showed a peak level at 24 hours (a 48-fold increase), gradually declined, and returned to the control level at 24 weeks. Western blot and immunohistochemistry demonstrated no expression of apoJ protein in noninjured aorta, an expression of apoJ at 2 days after balloon injury, and a peak level (a 55-fold increase) at 2 to 8 weeks. The expression of apoJ protein continued until 24 weeks after injury. In situ hybridization revealed that apoJ mRNA was expressed in smooth muscle cells (SMCs) of media at 2 days after injury and in SMCs of media and neointima at 2 weeks. To analyze the function of apoJ, stably transfected rabbit SMCs were created. The expression of apoJ stimulated proliferation and migration of SMCs. Conclusions-ApoJ is dramatically induced in media and neointima after vascular injury, suggesting that apoJ contributes to restenosis after angioplasty.