Fluid shear stress induces heat shock protein 60 expression in endothelialcells in vitro and in vivo

Recent investigations indicate that the initial event in the pathogenesis o f atherosclerosis involves an (auto)immunologic injury to the vessel wall. Heat shock proteins (hsps), which are expressed on the endothelial cell sur face, constitute possible autoantigens. After being exposed to shear stress of 30 dyne/cm(2) in vitro by means of a rotational viscometer, human umbil ical vein endothelial cells were immunohistochemically stained for hsp 60 b y the monoclonal antibody ML-30; static control cells were negative. Maxima l hsp 60 induction was observed after 12 hours of hemodynamic stress. In No rthern blots, the level of hsp 60 mRNA was markedly increased after only 1 hour of shear stress in human umbilical vein endothelial cells compared wit h static control cells. In vivo investigations in Lewis rats confirmed thes e in vitro findings: the intima and media of frozen sections of the right c ommon carotid artery exposed to increased wall shear stress (after ligation of the left common carotid artery) were stained for hsp 60; The vessel wal l of the left low-shear-stress-exposed side was negative. These findings de monstrate that shear stress results in hsp 60 induction in endothelial cell s in vivo and in vitro, providing the prerequisite for humoral and cellular reactions to endothelial hsp in the earliest stages of atherosclerosis.