TY - JOUR
T1 - Semicarbazide-sensitive amine oxidase and extracellular matrix deposition by smooth-muscle cells
AU - Langford, Shannon D.
AU - Trent, Margaret B.
AU - Boor, Paul J.
N1 - Funding Information:
The authors wish to express their gratitude to Dr. R. Fritz and the staff of the University of Texas Medical Branch Protein Chemistry Core Laboratory for their contributions to the completion of this study. We thank Dr. D. M. Palfreyman and Dr. E. H. W. Böhme of Marion Merrell Dow Research Institute for kindly supplying MDL-72274A and MDL-72145A. This work was supported by grants to S. D. Langford (National Institute of Environmental Health Sciences Toxicology Training grant T32ES07254, United States Environmental Protection Agency Fellowship U-915014-01-2, and the University of Texas Medical Branch Sealy Center on Aging grant 0-18311-644400-10) and to P. J. Boor (National Institutes of Health Grant AGI 8094, grant 8750 from the Shriners Hospital for Children, and University of Texas Medical Branch Sealy Center grant 2516-99). Although the research described in this article has been funded in part by the United States Environmental Protection Agency under the assistance agreement listed above, it has not been subjected to the EPA’s peer and administrative review and, therefore, may not necessarily reflect the views of the Agency, and no official endorsement should be inferred.
PY - 2002
Y1 - 2002
N2 - We have recently reported in vivo disruption of collagen and elastin architecture within blood vessel walls resulting from the selective inhibition of the enzyme semicarbazide-sensitive amine oxidase (SSAO). This study further investigates the effects of SSAO inhibition on extracellular matrix deposition by smooth-muscle cells (SMCs) cultured from neonatal rat hearts. SMCs were characterized, SSAO activity was measured, and soluble and insoluble collagen and elastin in the extracellular matrix (ECM) were quantified. Cultured neonatal rat heart SMC exhibited a monotypic synthetic phenotype that likely represents a myofibroblast. Detectable levels of SSAO activity present throughout 30-d culture peaked at 7-14 d, coinciding with the production of ECM. The addition of enzyme inhibitors and alternate SSAO substrates (benzylamine) produced varied and, in some cases, marked changes in SSAO activity as well as in the composition of mature and soluble matrix components. Similar to our previous in vivo findings, in vitro SSAO inhibition produced aberrations in collagen and elastin deposition by heart SMC. Because changes in SSAO activity are associated with cardiovascular pathologic states, this enzyme may play a protective or modulating role by regulating ECM production during pathologic insult.
AB - We have recently reported in vivo disruption of collagen and elastin architecture within blood vessel walls resulting from the selective inhibition of the enzyme semicarbazide-sensitive amine oxidase (SSAO). This study further investigates the effects of SSAO inhibition on extracellular matrix deposition by smooth-muscle cells (SMCs) cultured from neonatal rat hearts. SMCs were characterized, SSAO activity was measured, and soluble and insoluble collagen and elastin in the extracellular matrix (ECM) were quantified. Cultured neonatal rat heart SMC exhibited a monotypic synthetic phenotype that likely represents a myofibroblast. Detectable levels of SSAO activity present throughout 30-d culture peaked at 7-14 d, coinciding with the production of ECM. The addition of enzyme inhibitors and alternate SSAO substrates (benzylamine) produced varied and, in some cases, marked changes in SSAO activity as well as in the composition of mature and soluble matrix components. Similar to our previous in vivo findings, in vitro SSAO inhibition produced aberrations in collagen and elastin deposition by heart SMC. Because changes in SSAO activity are associated with cardiovascular pathologic states, this enzyme may play a protective or modulating role by regulating ECM production during pathologic insult.
KW - Extracellular matrix (ECM)
KW - Semicarbazide-sensitive amine oxidase (SSAO)
KW - Smooth-muscle cells (SMCs)
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U2 - 10.1385/CT:2:2:141
DO - 10.1385/CT:2:2:141
M3 - Article
C2 - 12271157
AN - SCOPUS:0036368582
SN - 1530-7905
VL - 2
SP - 141
EP - 150
JO - Cardiovascular toxicology
JF - Cardiovascular toxicology
IS - 2
ER -