Ruolo delle acetiltransferasi e deacetilasi istoniche nell'aterosclerosi

Atherosclerosis is one of the principal reason of death in the industrialized world. Laminar blood flow alterations seem to contribute to the physio-pathological environment that leads to atherogenesis. We have already described how laminar blood flow regulates chromatin remodeling in human endothelial cells, modifying specific histone residues. Recent observations suggest that laminar flow-dependent nitric oxide (NO) production could have a role in these phenomena stimulating the nuclear localization of class II HDACs in vascular cells, while inhibitors of nitric oxide production block this process. Western blot experiments performed on smooth muscle cells extracts, exposed to laminar flow and treated with NO inhibitors, show an enhancement in histone H3 acetylation when compared to control cells. These results indicate that NO plays an important role in chromatin remodeling. It is well known that alterations in NO production as wen as blood flow turbulence are particularly relevant in atherogenic prone regions. For this reason, the chromatin state of the cells that contribute to atherosclerotic plaques formation has been analyzed by immunohistochemistry. Our results show a significant enhancement in histone H3 acetylation and phosphorylation in smooth muscle cells in atherosclerotic regions compared to normal arteries. In conclusion, these data suggest that chromatin remodeling, mediated by blood flow alterations and NO production, may provide the molecular basis for the cellular activation associated to atherosclerosis.