Heat shock protein (HSP) 47 and collagen are upregulated during neointimal formation in the balloon-injured rat carotid artery.
Heat shock protein (HSP) 47, a collagen-specific molecular chaperone, is thought to be essential for the proper processing and secretion of procollagen molecules. We investigated the time course and localization of HSP47 and collagen expression after balloon catheter angioplasty in the rat carotid artery, based on the premise that accumulation of extracellular matrix components is a main feature of intimal hyperplasia in humans and in laboratory animals. Low levels of HSP47 expression were evident in uninjured carotid arteries. Northern blot analysis revealed that HSP47 mRNA expression was markedly stimulated 1--3 days after the induced injury and a high level was maintained for 7 days, followed by a gradual decline for up to 21 days after the injury. These changes in HSP47 expression paralleled changes in alpha 1(I) collagen expression. Immunohistochemical staining revealed colocalization of HSP47 and collagen in smooth muscle cells (SMCs) of the media and intima. In situ hybridization analysis showed that activated SMCs, which proliferated 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-beta was noted. These results show that SMCs activated after balloon injury express high levels of HSP47 and collagen during cell proliferation and migration, hence an overproduction of collagen and development of intimal thickening. Thus, HSP47 plays a role in the formation and progression of neointima after angioplasty.
Murakami
S
S
Medicinal Research Laboratories, Taisho Pharmaceutical Co. Ltd., Ohmiya 330-8530, Japan. s12867@ccm.taisho.co.jp
Toda
Y
Y
Seki
T
T
Munetomo
E
E
Kondo
Y
Y
Sakurai
T
T
Furukawa
Y
Y
Matsuyama
M
M
Nagate
T
T
Hosokawa
N
N
Nagata
K
K
D000818:Animals; D001011:Aorta / Q000166:cytology / Q000378:metabolism; D020212:Carotid Artery Injuries / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology*; D002404:Catheterization / Q000009:adverse effects*; D002478:Cells, Cultured; D003094:Collagen / Q000235:genetics / Q000378:metabolism*; D050958:HSP47 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution; D017539:Tunica Intima / Q000502:physiology*; D015854:Up-Regulation
D050958:HSP47 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D012333:RNA, Messenger; C494660:SERPINH1 protein, human; C494662:Serpinh1 protein, rat; D003094:Collagen