Serum‐Induced vascular smooth muscle cell elastolytic activity through tyrosine kinase intracellular signalling

Jun Kobayashi, Dennis Wigle, Tim Childs, Li Zhu, Fred W. Keeley, Marlene Rabinovitch

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34 Scopus citations

Abstract

In previous studies, we related increased elastolytic activity in pulmonary arteries (PA) with endothelial injury to the later development of PA hypertension in rats. As the mechanism causing the incrased PA elastase was unknown, we hypothesized that serum factors which are accessible to vascular smooth muscle cells (SMC) following endothelial injury stimulate their elastolytic activity. To test this, we developed an in vitro assay in which we added [3H]‐elastin to cultured vascular SMC after 24 h serum starvation and monitored elastolysis following a further 24 h incubation with fetal bovine serum (FBS). We observed that serum induced increased elastolytic activity in both PA and aorta‐derived SMC but not in endothelial cells or SMC with low basal levels of elastolytic activity. Maximum stimulation of SMC elastolytic activity occurred with a concentration as low as 1% FBS and despite elastase inhibitors in serum, suggesting that the activity is confined to the immediate pericellular region where enzyme concentration is high. Serum‐stimulated elastolytic activity was not reproduced by growth factors or cytokines known to be associated with vascular disease or to induce release of elastases in other cells. The serum inducing elastolytic activity was heat and acid labile. It was associated with increased elastin adhesion to the 67 kD elastin binding protein on SMC surfaces and was prevented by tyrosine kinase inhibitors but not protein kinase C or A inhibitors. Our studies therefore suggest a mechanism whereby serum induction of SMC elastase requires signalling through the elastin binding protein and activation of tyrosine kinase. © 1994 Wiley‐Liss, Inc.

Original languageEnglish (US)
Pages (from-to)121-131
Number of pages11
JournalJournal of Cellular Physiology
Volume160
Issue number1
DOIs
StatePublished - Jul 1994

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ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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