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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21:40.)
© 2001 American Heart Association, Inc.

Vascular Biology

HSP47 Expression by Smooth Muscle Cells Is Increased During Arterial Development and Lesion Formation and Is Inhibited by Fibrillar Collagen

Edward Rocnik; Laura Saward; J. Geoffrey Pickering

From the John P. Robarts Research Institute (Vascular Biology Group), London Health Science Centre, and the University of Western Ontario, Departments of Medicine (Cardiology), Biochemistry, and Medical Biophysics London, Ontario, Canada.

Correspondence to J. Geoffrey Pickering, MD, PhD, FRCP(C), London Health Science Centre, 339 Windermere Rd, London, Ontario N6A 5A5. E-mail gpickering{at}rri.on.ca

Abstract—HSP47 is a heat-shock protein that interacts with intracellular procollagen. It has been found in fibrous atherosclerotic plaque, but its involvement in acute vascular restructuring is unknown. We analyzed the expression of HSP47 and its regulation in the developing rat aorta and after balloon injury to the adult rat carotid artery. HSP47 was strongly expressed in each layer of the maturing fetal aorta (embryonic day 17 to birth). Expression declined during the first 4 postnatal days but persisted at low abundance into adulthood. HSP47 expression was substantially upregulated in the injured carotid artery, with intense immunostaining in neointimal smooth muscle cells (SMCs). HSP47 expression in SMCs was correlated with the emergence of a less mature phenotype and with expression of type I procollagen. Interestingly, a precipitous decline in HSP47 expression was evident during aortic development and after carotid artery injury, in association with the appearance of collagen fibrils in the local extracellular matrix. Furthermore, type I collagen fibrils, but not collagen monomers, inhibited expression of HSP47 by SMCs. These findings indicate that upregulation of HSP47 is a feature of vascular restructuring, including acute neointimal formation, and that the constituents of the extracellular matrix regulate the duration of expression. This feedback control may be important for self-termination of vascular development and lesion growth.

Key Words: smooth muscle cells • collagen • heat-shock protein • neointima • vascular development

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