461-P: Treatment with Mild Electrical Stimulation + Heat Shock (MET) Suppresses the Progression of Atherosclerosis in ApoE-Deficient Mice

Abstract

[Purpose] We have previously reported that mild electrical stimulation + heat shock (MET) treatment promotes the expression of heat shock protein 72 (HSP72), which works as molecular chaperone to suppresses oxidative stress, JNK activity and mitochondrial dysfunction, and thus ameliorates insulin resistance and hyperglycemia. Macrophage polarity and atherogensis with MET were investigated.[Methods] RAW264.7 and mouse bone marrow-derived macrophages (BMM) were treated with MET (42°C, 55 pulses/sec, 0.1 ms duration) and LPS 1 ng/mL. Six-week-old HSP+/+/ApoE-/- and HSP-/-/ApoE-/- mice were given a high-fat diet (HFD) for 14 weeks, and Sham/MET treatment was started from 10 weeks of age onwards. Glucose tolerance, biochemical parameters were examined, and the degree of arteriosclerosis (AS) formation and oxidative stress were evaluated histologically in aorta. [Results] After MET treatment in RAW264.7, HSP72 mRNA was increased, and LPS-stimulated MCP-1 and iNOS expression and JNK phosphorylation were all decreased. Experiment using BMM showed similar results with RAW264.7. There were no significant differences in physiologocal and metabolic parameters between Sham and MET groups after HFD. Compared with the MET group of HSP-/-/ApoE-/- mice, the degree of AS formation, necrotic core and fibrous capsule thickness were all significantly decreased in the MET group of HSP+/+/ApoE-/- mice. However, no beneficial effects were observed either in Sham or MET in HSP-/-/ApoE-/- mice. Immunostaining of the plaque showed significant suppression of 4-HNE and F4/80 in the HSP+/+/ApoE-/- mice treated with MET compared to those with Sham. Neither Sham nor MET had an inhibitory effect of 4-HNE and F4/80 in HSP-/-/ApoE-/- mice.[Conclusion] The enhancement of HSP72 expression by MET showed anti-inflammatory effect by polarity changes in macrophages and suppression of oxidative stress, which may lead to the suppression of atherosclerosis. Disclosure R.Yoshizumi: None. T.Kondo: None. T.Watanabe: None. N.Miyakawa: None.