Phenotype dictates the growth response of vascular smooth muscle cells to pulse pressure in vitro

Exp Cell Res. 1999 Jul 10;250(1):174-86. doi: 10.1006/excr.1999.4502.

Abstract

The objective of this study was to determine the effect of phenotype on pulse pressure-induced signaling and growth of vascular smooth muscle cells in vitro. Using a perfused transcapillary culture system, cells were exposed to increases in pulsatile flow and hence pulse pressure and maintained for 72 h before cells were harvested. Cell proliferation was determined by cell number, DNA synthesis, and proliferating cell nuclear antigen expression. Mitogen-activated protein kinase (MAPK) levels were determined by immunoblot and kinase activity by phosphorylation of myelin basic protein. Cell phenotype was determined by immunoblot and immunocytofluorescence using antisera specific for the differentiation markers alpha-actin, myosin, calponin, osteopontin, and phospholamban. In cells that highly expressed these differentiation markers, there was a significant increase in cell growth in response to chronic increases in pulse pressure without a significant change in MAPK activity in these cells. In contrast, in cells that weakly expressed SMC differentiation markers, there was a significant decrease in cell growth concomitant with a significant decrease in MAPK signaling in these cells. We conclude that SMC phenotype dictates the growth response of SMC to mechanical force in vitro.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Actins / analysis
  • Animals
  • Calcium-Binding Proteins / analysis
  • Calcium-Calmodulin-Dependent Protein Kinases / biosynthesis
  • Cattle
  • Cell Division
  • DNA / biosynthesis
  • Electric Stimulation
  • MAP Kinase Kinase 1
  • MAP Kinase Kinase 2
  • Male
  • Microfilament Proteins
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinase Kinases*
  • Mitogen-Activated Protein Kinases*
  • Mitogens
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / metabolism
  • Muscle, Smooth, Vascular / physiology*
  • Myosins / analysis
  • Osteopontin
  • Phenotype
  • Physical Stimulation
  • Proliferating Cell Nuclear Antigen / biosynthesis
  • Protein-Serine-Threonine Kinases / biosynthesis
  • Protein-Tyrosine Kinases / biosynthesis
  • Pulsatile Flow*
  • Rats
  • Rats, Sprague-Dawley
  • Sialoglycoproteins / analysis
  • Signal Transduction*

Substances

  • Actins
  • Calcium-Binding Proteins
  • Microfilament Proteins
  • Mitogens
  • Proliferating Cell Nuclear Antigen
  • Sialoglycoproteins
  • Spp1 protein, rat
  • calponin
  • phospholamban
  • Osteopontin
  • DNA
  • Protein-Tyrosine Kinases
  • Protein-Serine-Threonine Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 1
  • MAP Kinase Kinase 2
  • Mitogen-Activated Protein Kinase Kinases
  • Myosins