Proliferative synergy of ANG II and EGF in porcine aortic vascular smooth muscle cells

S. P. Bagby, E. A. Kirk, L. H. Mitchell, M. M. O'Reilly, W. E. Holden, P. E. Stenberg, A. C. Bakke

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

To test growth effects of angiotensin II (ANG II) in porcine vascular smooth muscle cells (VSMC) and potential ANG II synergy with epidermal growth factor (EGF), we exposed subconfluent, near-quiescent porcine aortic VSMC to ANG II, EGF, or ANG II + EGF (each 10-9 M) in Dulbecco's modified Eagle's- Ham's F-12 medium with insulin + 0.4% fetal calf serum (FCS) selected for minimal ANG II-degrading capacity. Cell number and DNA and protein synthesis (by [3H]-thymidine and [35S]methionine incorporation, respectively) were determined serially over 1-6 days. ANG II alone induced an early 20% increase and then a plateau in cell number over the 0.4% FCS control (P < 0.01; n = 8), thus without sustained increase in proliferation rate. Yet ANG II alone did not increase fractional DNA or protein synthesis (each as cpm/103 cells) and, by flow cytometry, reduced S phase fraction without increase in cell size. EGF alone induced brisk DNA synthesis yet minimal cell division over days 0-4, thus late-cycle arrest. ANG II + EGF, despite no increase in fractional DNA or protein synthesis rates over EGF alone, induced significant indomethacin-resistant dose-dependent (P < 0.001) increase in cell proliferation rate over EGF alone with a median effective dose of 5 x 10- 10 M ANG II, thus proliferative synergy. We propose that 1) ANG II induces a subpopulation of cells arrested in or beyond S phase to proceed through mitosis but does not influence G1 traversal or S phase entry and 2) ANG II + EGF achieve proliferative synergy by complementary actions at sequential cell cycle loci, with EGF supporting progression from G0/G1 to S phase and ANG II inducing completion of mitosis by cells already in or beyond S phase ('late-cycle completion').

Original languageEnglish (US)
Pages (from-to)F239-F249
JournalAmerican Journal of Physiology - Renal Fluid and Electrolyte Physiology
Volume265
Issue number2 34-2
StatePublished - Jan 1 1993

    Fingerprint

Keywords

  • cell cycle analysis
  • cell size
  • deoxyribonucleic acid synthesis
  • flow cytometry
  • hydrogen-3-labeled thymidine incorporation
  • hyperplasia
  • hypertrophy
  • indomethacin
  • losartan
  • protein synthesis
  • sulfur-35-labeled methionine incorporation
  • vascular growth

ASJC Scopus subject areas

  • Physiology

Cite this

Bagby, S. P., Kirk, E. A., Mitchell, L. H., O'Reilly, M. M., Holden, W. E., Stenberg, P. E., & Bakke, A. C. (1993). Proliferative synergy of ANG II and EGF in porcine aortic vascular smooth muscle cells. American Journal of Physiology - Renal Fluid and Electrolyte Physiology, 265(2 34-2), F239-F249.