Thermal Treatment Attenuates Neointimal Thickening With Enhanced Expression of Heat-Shock Protein 72 and Suppression of Oxidative Stress

Abstract

Background-The beneficial effects of thermal therapy have been reported in several cardiovascular diseases. However, it is unknown whether the thermal treatment has some beneficial roles against the development of atherosclerosis. Methods and Results-The inflammatory arterial lesion was introduced by placement of a polyethylene cuff on femoral arteries of male Sprague-Dawley rats for 4 weeks. Thermal-treated group underwent daily bathing in 41°C hot water for 15 minutes. Neointimal thickening along with immunohistochemical expression of heat-shock proteins (HSPs), monocyte chemoattractant protein-1 (MCP-1), and NADPH oxidase were compared with those of a thermally untreated (Control) group. Morphometric analysis demonstrated a significant suppression of neointimal thickening in thermal-treated group compared with the Control group (intimal/medial area ratios, 0.01Ϯ0.01 versus 0.31Ϯ0.04, PϽ0.01). Expression of MCP-1 and infiltration of ED-positive cells were enhanced in the adventitial layer of Control. More importantly, expression of HSP72 in media was enhanced by thermal treatment. Expression of p22-phox, the major membrane subunit of NADPH oxidase, and MCP-1 was augmented in cuff-injured adventitia of the Control but not the thermal-treated groups. Conclusions-Thermal treatment significantly attenuated infiltration of inflammatory cells in adventitia and suppressed neointimal thickening in cuff-injured arteries with the enhancement of HSP72 expression and suppression of oxidative stress.

Endothelial nitric oxide synthase induces heat shock protein HSPA6 (HSP70B′) in human arterial smooth muscle cells

“…Some of these regulators can reduce atherosclerosis via preventing neo intimal hyperplasia. Relevant to the current study is the observation that heat treatment can inhibit neo-intima growth [31][32][33]. Interestingly, elevation in HSP72 (which has high homology with HSPA6) has been associated with the heat shock reduction in smooth muscle cell proliferation after trauma [31].…”

“…Interestingly, elevation in HSP72 (which has high homology with HSPA6) has been associated with the heat shock reduction in smooth muscle cell proliferation after trauma [31]. Two studies demonstrated that thermal treatment of arterial tissues in vitro and in vivo caused a reduction in media growth, leading to a prevention of arterial restenosis [33,34]. In one study hyperthermia at 43 o C was effective in suppressing rat vascular SMC proliferation in vitro by causing cell cycle arrest without causing cell death and not affecting endothelial cells which are normally damaged after angioplasty [34].…”

“…In one study hyperthermia at 43 o C was effective in suppressing rat vascular SMC proliferation in vitro by causing cell cycle arrest without causing cell death and not affecting endothelial cells which are normally damaged after angioplasty [34]. In the second study thermal treatment of cuff injured rat arteries in vivo inhibited neo-intimal thickening in association with increased HSP72 expression [33].…”

Effects of Removing the Adventitia on the Mechanical Properties of Ovine Femoral Arteries In Vivo and In Vitro

“…1 However, recent findings suggest that the adventitia is an active layer that could play an important role in the physiological regulation of arterial smooth muscle tone, 2-5 modulating the response to stimuli such as noradrenalin and angiotensin II, and regulating nitric oxide release from the endothelium, thus counterbalancing the vasoconstrictor effects on smooth muscle cells. 6 An active role of the adventitia in determining arterial properties has been proposed in pathological states such as atherosclerosis 7 and systemic hypertension, 8 and in arterial wall remodeling. 2,9, 10 …”

Targeting Molecular Chaperones in Diabetic Peripheral Neuropathy

“…In this study, heat therapy on patients with type 2 DM through hot tub immersion six days a week for three consecutive weeks dropped their fasting plasma glucose and mean glycosylated hemoglobin levels (Hooper, 1999). Although the HSP levels were not measured in this trial, it documented an average rise of 0.8°C in body temperature, which is sufficient for HSP induction (Okada et al, 2004). Despite the lack of proper controls and its exploratory nature, the credibility of this early report has been substantiated by similar studies from animal models of DM.…”