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 a s a chaperone for procollagen. Its involvement in atherosclerosis is unknow n. Methods and Results-Hsp47 expression in human coronary arteries was assesse d by immunostaining. Strong focal expression was evident in atherosclerotic , but not normal, arteries and was prevalent in the collagenous regions. Do uble immunostaining revealed that all cells expressing type I procollagen a lso expressed Hsp47, Moreover, parallel regulation of pro alpha 1(I)collage n and Hsp47 mRNA expression occurred with cultured human smooth muscle cell s stimulated with transforming growth factor-beta 1 or fibroblast growth fa ctor-2, However, a proportion of Hsp47-expressing cells in plaque did not e xpress type I procollagen, and this pattern could be reproduced in culture. Heat shock and oxidized LDL stimulated the expression of Hsp47 mRNA by smo oth muscle cells, without a concomitant rise in pro alpha 1(I)collagen expr ession. Conclusions-These findings identify Hsp47 as a novel constituent of human c oronary 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 stabili ty.