Heat shock protein (HSP) 47 and collagen are upregulated during neointimalformation in the balloon-injured rat carotid artery

Heat shock protein (HSP) 47, a collagen-specific molecular chaperone, is th ought to be essential for the proper processing and secretion of procollage n molecules. We investigated the time course and localization of HSP47 and collagen expression after balloon catheter angioplasty in the rat carotid a rtery, based on the premise that accumulation of extracellular matrix compo nents is a main feature of intimal hyperplasia in humans and in laboratory animals. Low levels of HSP47 expression were evident in uninjured carotid a rteries. Northern blot analysis revealed that HSP47 mRNA expression was mar kedly stimulated 1-3 days after the induced injury and a high level was mai ntained for 7 days, followed by a gradual decline for up to 21 days after t he injury. These changes in HSP47 expression paralleled changes in al(I) co llagen expression. Immunohistochemical staining revealed colocalization of HSP47 and collagen in smooth muscle cells (SMCs) of the media and intima. I n situ hybridization analysis showed that activated SMCs, which proliferate d and migrated into the intima, expressed high levels of HSP47. In cultured human aortic SMCs. similar upregulation of HSP47 and alpha1(I) collagen by TGF-P was noted. These results show that SMCs activated after balloon inju ry express high levels of HSP47 and collagen during cell proliferation and migration, hence an overproduction of collagen and development of intimal t hickening. Thus, HSP47 plays a role in the formation and progression of neo intima after angioplasty. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.