© 1997 American Heart Association, Inc.
Articles |
PDGF Receptor Protein Tyrosine Kinase Expression in the Balloon-Injured Rat Carotid Artery
From the Department of Vascular and Cardiac Diseases, Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Company, Ann Arbor, Mich.
Correspondence to Robert L. Panek, PhD, Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Co, 2800 Plymouth Rd, Ann Arbor, MI 48105.
Abstract Platelet-derived growth factor (PDGF) receptor
gene expression has previously been demonstrated in balloon-injured rat
carotid arteries to be regulated during repair of carotid injury. In
the present study we showed that PDGF receptor protein expression
and phosphorylation are changed over time after carotid
artery injury. In control and 2-day-postinjury vessels, expression of
PDGF 
receptor protein was readily detectable, whereas PDGF ß
receptor expression appeared very low. Between 2 and 7 days postinjury,
a time interval previously shown to correspond with smooth muscle cell
migration followed by the appearance of a neointima, PDGF
receptor expression had increased only slightly, to roughly 35%
above control levels, and was maximal by day 7 postinjury, whereas PDGF
ß receptor expression had doubled. From 7 to 14 days after carotid
injury, intimal area was greatly increased and was associated with a
further increase in PDGF ß receptor protein expression and receptor
phosphorylation to a maximum between days 10 and 12. In
contrast, PDGF receptor expression had decreased slightly during
this time interval. Moreover, phosphorylation of PDGF
receptors was barely detectable and did not change over the time
course of injury. From 14 to 28 days after injury, intimal area was
increased only slightly, whereas PDGF ß receptor protein and
phosphorylation levels had diminished to roughly half
of the 10-day injury values. In addition, the increases in PDGF ß
receptor protein expression and tyrosine
phosphorylation observed over the time of injury were
also associated with a corresponding increase in the association of
phosphatidylinositol 3' kinase (PI-3 kinase) with
phosphorylated PDGF ß receptors. These findings show
that balloon injury to rat carotid arteries results in temporally
related changes in the expression of PDGF receptors and their state of
tyrosine phosphorylation. Furthermore, tyrosine
phosphorylation of PDGF ß receptors in the
balloon-injured rat carotid artery in vivo resulted in the association
of PI-3 kinase. These are important new findings, which add to our
knowledge concerning the role and activity of PDGF receptors in the
formation of a neointima.
Key Words: PDGF receptors • tyrosine phosphorylation • carotid artery injury • PI-3 kinase
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