Development-related changes in matrix metalloproteinase expression in human aortic smooth muscle cells.
BACKGROUND
It is known that extracellular matrix-degrading enzymes play an important role in tissue remodeling and that large amounts of structural proteins including types I, III, IV, and V collagens and elastin are produced by smooth muscle cells (SMC) in the arterial wall. We have recently shown that matrix metalloproteinases (MMPs) produced by human aortic medial smooth muscle cells are closely related to the proliferation of the cells, leading to the formation of atherosclerotic plaques, characteristic of intimal remodeling. For a better understanding of the mechanism of atherogenesis, therefore, it is important to clarify the relationship between the production of matrix-degrading enzymes and artery development.


METHODS
In vivo or in vitro synthesis of MMPs by SMC was analyzed by immunohistochemistry and immunoblotting. Elastase activity in the culture medium was also estimated.


RESULTS
Production of proMMP 1, 2, and 3 was detected in cultured SMC isolated from the aortas of both neonates and fetuses; in medial SMC cultured from young individuals, production of proMMP-1 and -3 was extremely decreased, but was apparent in intimal SMC. Immunohistochemical observation indicated that in the media of fetal or neonatal aorta, SMC synthesized large amounts of the three proMMPs; in aortas from older individuals, proMMP-2, but not proMMP-1 and -3, was detected in the media, and relatively large amounts of proMMP-1, -2, and -3 were produced by SMC in the slightly thickened intima. Assay of elastase activity in the culture medium gave results similar to those for MMPs.


CONCLUSIONS
We conclude that the production of proMMP-1 and -3 is associated with phenotypic modulation of SMC to a "synthetic" state, and that the ability of SMC to produce MMPs plays an important role in the development and/or aging of the human aorta through remodeling of the extracellular matrix; furthermore elastase is also involved in these processes in the arterial wall.
Sasaguri
Y
Y
Department of Pathology, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan.
Murahashi
N
N
Sugama
K
K
Kato
S
S
Hiraoka
K
K
Satoh
T
T
Isomoto
H
H
Morimatsu
M
M
D000293:Adolescent; D000328:Adult; D000375:Aging / Q000378:metabolism*; D001011:Aorta / Q000166:cytology / Q000201:enzymology*; D002478:Cells, Cultured; D002648:Child; D005109:Extracellular Matrix / Q000201:enzymology*; D005260:Female; D005333:Fetus / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D007231:Infant, Newborn; D008297:Male; D008666:Metalloendopeptidases / Q000378:metabolism*; D008854:Microscopy, Electron; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000201:enzymology*
D008666:Metalloendopeptidases