Heat shock protein 65 increases arterial contractility which can be reversed with Mycobacterium vaccae

Abstract

Introduction. An association has been shown between raised serum antibody levels to 65 kDa heat-shock protein (Hsp65) and vascular diseases suggesting that it might play a role in its pathogenesis. It was the aim of this study to investigate the effects of Hsp65 on the vasculature. Methods. Male Dark Agouti rats were either immunised with 200 gg Hsp 65 kDa in Freunds Incomplete Adjuvant on day 14 only (Hsp group) or with 10' Mycobacterium vaccae on day 0 and Hsp65 on day 14 (My group). Six rats were used as controls. Four animals were sacrificed at 4 weeks following immunization, the others, including the control, after 10 weeks. Rings of thoracic aorta were assessed for contraction and relaxation in response to phenylephrine and acetylcholine using an organ bath technique. The distal thoracic aorta was used for histology to determine intima/media thickness. Thl/Th2 status (IFNy/IL-10) was also assessed using flow cytometry. Results.The Hsp group showed significantly increased contractility both at 4 and 10 weeks. In the MV group at 4 weeks, contractility was significantly decreased, but rose again after 10 weeks. The dose-response curve for relaxation in both groups was not significantly different from the control, suggesting intact endothelial nitric oxide synthesis. No significant difference could be found in intima/media thickness in both groups. The cytokine expression was shifted from Thl towards a Th2 status at 4 weeks in the Hsp group. The MV group, however, showed a shift from Th2 to Thl1 status at 4 weeks. Both were reversed again after 10 weeks. Conclusions. This study has shown a change in vasocontractility produced by immunization with Hsp65; short-term this could be reversed with MV. Similar short-term changes could be seen in the Thl1/Th2 status. This novel finding may have implications for understanding the aetiology of vasospastic disorders and may open new ideas for therapeutic strategies modifying the Th I /Th2 status in vascular patients.