Heat shock protein 47 is expressed in fibrous regions of human atheroma and Is regulated by growth factors and oxidized low-density lipoprotein.
BACKGROUND
Heat shock protein 47 (Hsp47) is a stress protein that may act as a chaperone for procollagen. Its involvement in atherosclerosis is unknown.


RESULTS
Hsp47 expression in human coronary arteries was assessed by immunostaining. Strong focal expression was evident in atherosclerotic, but not normal, arteries and was prevalent in the collagenous regions. Double immunostaining revealed that all cells expressing type I procollagen also expressed Hsp47. Moreover, parallel regulation of proalpha1(I)collagen and Hsp47 mRNA expression occurred with cultured human smooth muscle cells stimulated with transforming growth factor-beta1 or fibroblast growth factor-2. However, a proportion of Hsp47-expressing cells in plaque did not express type I procollagen, and this pattern could be reproduced in culture. Heat shock and oxidized LDL stimulated the expression of Hsp47 mRNA by smooth muscle cells, without a concomitant rise in proalpha1(I)collagen expression.


CONCLUSIONS
These findings identify Hsp47 as a novel constituent of human coronary atheroma. Its localization to the fibrous cap, regulation by growth factors in parallel with type I procollagen, and selective upregulation by stress raise the possibility that Hsp47 is a determinant of plaque stability.
Rocnik
E
E
John P. Robarts Research Institute (Vascular Biology Group), London Health Sciences Centre, London, Ontario, Canada.
Chow
L H
LH
Pickering
J G
JG
D000293:Adolescent; D000328:Adult; D000368:Aged; D001158:Arteries / Q000378:metabolism / Q000473:pathology; D001161:Arteriosclerosis / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology / Q000502:physiology*; D050958:HSP47 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008077:Lipoproteins, LDL / Q000502:physiology*; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D011347:Procollagen / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D012016:Reference Values; D014018:Tissue Distribution; D016212:Transforming Growth Factor beta / Q000494:pharmacology / Q000502:physiology*
D050958:HSP47 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D008077:Lipoproteins, LDL; D011347:Procollagen; D012333:RNA, Messenger; C494660:SERPINH1 protein, human; D016212:Transforming Growth Factor beta; C099252:oxidized low density lipoprotein; D016222:Fibroblast Growth Factor 2; D003094:Collagen