Early proto-oncogene expression in rat aortic smooth muscle cells following endothelial removal

J. M. Miano, R. R. Tota, N. Vlasic, K. J. Danishefsky, M. B. Stemerman

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Abstract

To study the mechanism(s) of vascular smooth muscle cell proliferation in vivo, mRNA levels of c-fos, c-jun, and c-myc were determined by Northern blot analysis following vascular balloon de-endothelialization (BDE). Medial smooth muscle cells (SMC) were separated and studied by enzymatic digestion of the vessel wall. mRNA levels of c-fos and c-jun from aortic smooth muscle cells (SMC) were simultaneously induced within 30 minutes of BDE and declined to baseline by 1.5 hours. c-myc mRNA did not begin to increase until hour after vascular injury. Levels of c-myc peaked at 2 hours and were sustained for additional 4 hours before gradually declining. Smooth muscle cells derived from enzyme-treated control aortae that did not undergo BDE expressed c-fos and c-jun, but showed no evidence of c-myc message. In contrast, nonenzymatically treated, non-BDE whole aortae (containing both media and adventitia) demonstrated a prominent c-myc signal, but failed to express c-fos and c-jun. Corresponding examination of adventitia derived from enzyme-treated aortae showed this tissue to be a source of all three proto-oncogenes. The results of this study demonstrate the earliest in vivo molecular markers of vascular injury reported to date and implicate SMC proto-oncogene expression in the initiation of SMC proliferation. Furthermore these findings suggest two avenues for protooncogene induction, that are due to (1) vessel wall manipulation and (2) humoral stimulation.

Original languageEnglish (US)
Pages (from-to)761-765
Number of pages5
JournalAmerican Journal of Pathology
Volume137
Issue number4
StatePublished - Jan 1 1990
Externally publishedYes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Miano, J. M., Tota, R. R., Vlasic, N., Danishefsky, K. J., & Stemerman, M. B. (1990). Early proto-oncogene expression in rat aortic smooth muscle cells following endothelial removal. American Journal of Pathology, 137(4), 761-765.