Heat shock proteins (HSP) are a family ofproteins present in the majority of cells and are produced s a cell protection mechanism against adverse conditions. HSP are present in both atherosclerotic plaques and healthy arteries, although their role in atherosclerosis remain to be defined. Our objective was to investigate the effect of HSP90 inhibitors in the modulation of the different processes involved in atherogenesis. We have used an HSP90 inhibitor (17-AAG), which is able to increase the heat shock response. Treatment of monocytes and vascular smooth muscle cells with 17-AAG increased HSP70 expression. Under these conditions, 17-AAG was able to decrease NADPH oxidase activity induced by TNF-α. Stimulation of cells with cytokines induced the activation of different signalling pathways (e.g. MAPKs and NF-κB) and increased the levels of cytokines such as IL-6, which was diminished by HSP90 inhibitors. Finally, while treatment with 17-AAG prevented the apoptosis of cells induced proapoptotic stimuli, HSP27 silencing increased apoptosis induced by elastase. HSP90 inhibitors decrease pro-atherogenic processes, suggesting that these drugs may have beneficial effects in the treatment of atherosclerosis.
- Heat shock proteins
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
- Pharmacology (medical)