Plasminogen activator expression in rat arterial smooth muscle cells depends on their phenotype and is modulated by cytokines

Autor: Michael S. Pepper, Marie-Luce Bochaton-Piallat, Giulio Gabbiani
Rok vydání: 1998
Předmět:
Platelet-Derived Growth Factor/pharmacology
Platelet-derived growth factor
Physiology
medicine.medical_treatment
Basic fibroblast growth factor
Becaplermin
Fibroblast Growth Factor 2/pharmacology
Cytokines/ pharmacology
Biology
ddc:616.07
Tissue plasminogen activator
Muscle
Smooth
Vascular
chemistry.chemical_compound
Plasminogen Activators
Muscle
Smooth
Vascular/drug effects/ metabolism
Transforming Growth Factor beta
Plasminogen Activator Inhibitor 1
medicine
Animals
Northern blot
Cells
Cultured
Platelet-Derived Growth Factor
T-plasminogen activator
Plasminogen Activators/ biosynthesis
Proto-Oncogene Proteins c-sis
musculoskeletal system
Molecular biology
Rats
Cytokine
Phenotype
chemistry
Cell culture
Transforming Growth Factors
Immunology
Transforming Growth Factors/pharmacology
cardiovascular system
Cytokines
Fibroblast Growth Factor 2
Cardiology and Cardiovascular Medicine
Plasminogen Activator Inhibitor 1/pharmacology
Plasminogen activator
Transforming Growth Factor beta/pharmacology
medicine.drug
Zdroj: Circulation Research, Vol. 82, No 10 (1998) pp. 1086-1093
ISSN: 0009-7330
Popis: Abstract —Cultured rat aortic smooth muscle cells (SMCs) exhibit at least 2 phenotypic variants: (1) a spindle-shaped phenotype, obtained from normal adult media, and (2) an epithelioid phenotype, obtained from intimal thickening 15 days after endothelial injury. Both phenotypes can be cloned from each location, with normal media yielding a majority of spindle-shaped clones and intimal thickening yielding a majority of epithelioid clones. These findings suggest that intimal thickening develops essentially from a subpopulation of medial SMCs exhibiting epithelioid features in vitro. Using zymographic and Northern blot analyses, we have studied plasminogen activator (PA) expression by these SMCs. Our results show that epithelioid SMCs, cultured as whole SMC populations or as clones, display higher PA activity than do spindle-shaped SMCs, irrespective of their origin. This is mainly due to differences in the expression of tissue PA and, to a lesser extent, urokinase PA and is accompanied by a decrease in PA inhibitor 1. Tissue PA activity is increased by basic fibroblast growth factor and platelet-derived growth factor-BB, particularly in epithelioid SMCs. Taken together, these results indicate that SMCs are heterogeneous with respect to their proteolytic profile, at least as far as the PA system is concerned. Proteolytic activity of the different SMC populations is modulated by cytokines that play a role in intimal thickening. Our results are in agreement with the suggestion that epithelioid SMCs are mainly responsible for intimal thickening.
Databáze: OpenAIRE
Externí odkaz: