HSP47 expression by smooth muscle cells is increased during arterial development and lesion formation and is inhibited by fibrillar collagen.
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.
Rocnik
E
E
John P. Robarts Research Institute (Vascular Biology Group), London Health Science Centre, University of Western Ontario, Canada.
Saward
L
L
Pickering
J G
JG
D000818:Animals; D000831:Animals, Newborn; D001011:Aorta / Q000196:embryology / Q000254:growth & development* / Q000378:metabolism / Q000473:pathology*; D002404:Catheterization; D002454:Cell Differentiation; D003094:Collagen / Q000502:physiology*; D005333:Fetus; D050958:HSP47 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D024510:Muscle Development; D009131:Muscle, Smooth, Vascular / Q000196:embryology / Q000254:growth & development* / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017539:Tunica Intima / Q000254:growth & development / Q000473:pathology
D050958:HSP47 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C494662:Serpinh1 protein, rat; D003094:Collagen