Semicarbazide-sensitive amine oxidase and extracellular matrix deposition by smooth-muscle cells.
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.
Langford
Shannon D
SD
Wyle Laboratories, Cellular Biotechnology-Flight Definition, NASA Johnson Space Center, Houston, TX 77058, USA.
Trent
Margaret B
MB
Boor
Paul J
PJ
D000498:Allyl Compounds / Q000008:administration & dosage / Q000037:antagonists & inhibitors; D000499:Allylamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors; D006631:Amine Oxidase (Copper-Containing) / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D003094:Collagen / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004549:Elastin / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D023421:Models, Animal; D008955:Models, Cardiovascular; D008996:Monoamine Oxidase Inhibitors / Q000008:administration & dosage; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000145:classification / Q000187:drug effects / Q000378:metabolism*; D011437:Propylamines / Q000008:administration & dosage / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D000498:Allyl Compounds; D004791:Enzyme Inhibitors; C090015:MDL 72274A; D008996:Monoamine Oxidase Inhibitors; D011437:Propylamines; D000499:Allylamine; C040051:2-(3,4-dimethoxyphenyl)-3-fluoroallylamine; D003094:Collagen; D004549:Elastin; D006631:Amine Oxidase (Copper-Containing)