Impaired fibrinolysis-inducing capacity for postinjury phenotype of cultivated human arterial and human atherosclerotic intimal smooth muscle cells.
Impaired fibrinolysis is believed to promote atherosclerosis and contribute to myocardial infarction. The major triggering factor for fibrinolysis is vascular tissue plasminogen activator (t-PA), and the aim of this study was to evaluate the capacity of human arterial smooth muscle cells (SMC) for induction of fibrinolysis. SMC were plated on labeled fibrin gels, and lysis was measured as release of label. Fibrinolytic capacity was dependent on the phenotypic state of SMC. The "multilayered phenotype" to which SMC modulate after cellular injury had a much lower fibrinolysis-inducing capacity than the more ordinary "monolayered" SMC type. Fibrinolysis was mediated by activation of plasminogen. In long-term experiments under conditions imitating thrombolysis, platelet-derived growth factor promoted fibrinolysis indirectly by increase of SMC number, and a direct effect on cellular production of t-PA was not detected. SMC from atherosclerotic intima had a much lower capacity for induction of fibrinolysis than cells from adjacent nonatherosclerotic intima. SMC also displayed several structurally detectable interactions with the fibrin substratum, such as organization of the gel by means of extension of numerous filamentous processes and contraction and wrinkling of the gel. In conclusion, human arterial SMC in vitro induce fibrinolysis by activation of plasminogen. This capacity is dependent on phenotype and lowered for SMC from atherosclerotic intima, suggesting impairment after arterial injury and in atherosclerosis.
Björkerud
S
S
Department of Pathology I, University of Göteborg, Sweden.
D001158:Arteries / Q000473:pathology; D001161:Arteriosclerosis / Q000473:pathology*; D002478:Cells, Cultured; D005342:Fibrinolysis; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000473:pathology*; D010641:Phenotype; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology
D010982:Platelet-Derived Growth Factor