Fluid shear stress induces heat shock protein 60 expression in endothelial cells in vitro and in vivo.
Recent investigations indicate that the initial event in the pathogenesis of atherosclerosis involves an (auto)immunologic injury to the vessel wall. Heat shock proteins (hsps), which are expressed on the endothelial cell surface, constitute possible autoantigens. After being exposed to shear stress of 30 dyne/cm(2) in vitro by means of a rotational viscometer, human umbilical vein endothelial cells were immunohistochemically stained for hsp 60 by the monoclonal antibody ML-30; static control cells were negative. Maximal hsp 60 induction was observed after 12 hours of hemodynamic stress. In Northern blots, the level of hsp 60 mRNA was markedly increased after only 1 hour of shear stress in human umbilical vein endothelial cells compared with static control cells. In vivo investigations in Lewis rats confirmed these in vitro findings: the intima and media of frozen sections of the right common carotid artery exposed to increased wall shear stress (after ligation of the left common carotid artery) were stained for hsp 60. The vessel wall of the left low-shear-stress-exposed side was negative. These findings demonstrate that shear stress results in hsp 60 induction in endothelial cells in vivo and in vitro, providing the prerequisite for humoral and cellular reactions to endothelial hsp in the earliest stages of atherosclerosis.
Hochleitner
B W
BW
Institute of Biomedical Aging Research, Austrian Academy of Sciences, Innsbruck, Austria. Boris.Hochleitner@uibk.ac.at
Hochleitner
E O
EO
Obrist
P
P
Eberl
T
T
Amberger
A
A
Xu
Q
Q
Margreiter
R
R
Wick
G
G
D000818:Animals; D001161:Arteriosclerosis / Q000235:genetics / Q000276:immunology*; D001324:Autoantigens / Q000235:genetics; D001794:Blood Pressure; D015152:Blotting, Northern; D017536:Carotid Artery, Common / Q000166:cytology / Q000503:physiopathology; D002478:Cells, Cultured; D018834:Chaperonin 60 / Q000032:analysis / Q000235:genetics* / Q000276:immunology*; D003470:Culture Media / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000737:chemistry / Q000166:cytology / Q000276:immunology*; D005260:Female; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D008026:Ligation; D010477:Perfusion; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011917:Rats, Inbred Lew; D013194:Staining and Labeling; D013314:Stress, Mechanical; D014471:Umbilical Veins / Q000166:cytology; D014783:Viscosity
D001324:Autoantigens; D018834:Chaperonin 60; D003470:Culture Media; D012333:RNA, Messenger