Low plasma levels of HSP70 in patients with carotid atherosclerosis are associated with increased levels of proteolytic markers of neutrophil activation

Abstract

Background and objective Low levels of circulating HSP70 have been correlated with a high risk of coronary artery disease. We have measured HSP70 concentrations in carotid atherosclerotic patients and we have investigated the biological significance of the inverse relation between HSP70 levels and atherosclerosis. Methods and results More HSP70 was released by healthy endarteries than by carotid atherosclerotic plaques, which was paralleled by a decrease in HSP70 plasma levels of patients with atherosclerosis relative to healthy subjects (ELISA). In contrast, elastase levels (ELISA) and activity (zymography) followed the opposite trend. HSP70 was proteolyzed when incubated with elastase in vitro or with atherosclerotic plaque samples, ex vivo, and this effect was prevented by elastase inhibitors (Western-blot). Finally, the levels of two markers of polymorphonuclear neutrophil activation (myeloperoxidase and matrix metalloproteinase-9/neutrophil gelatinase-associated lipocalin) followed a similar trend to that observed for elastase (ELISA), and a tight positive correlation existed between all three markers in conditioned media and in plasma. Conclusion Low plasma levels of HSP70 are found in patients with atherosclerosis. Activated neutrophils could play a major role as a source of proteases able to degrade atheroprotective HSP70.