VASCULAR SMOOTH MUSCLE AND MONOCYTE RECRUITMENT

  • Valente, Anthony J (PI)

Project: Research project

Project Details

Description

The overall aim of this project is to fully characterize the monocyte
chemoattractant SMC-CF, which is secreted by baboon aortic smooth muscle
cells (SMC) and which may regulate the intimal recruitment of blood
monocytes in atherogenesis. This potent chemoattractant is associated with
a low molecular weight (12-16 kD) basic monomeric protein which has been
successfully purified to homogeneity. Baboon SMC express the c-sis gene,
which encodes one of the two polypeptide chains of platelet-derived growth
factor (PDGF), a potent mitogen for SMC. PDGF in both its monomeric and
dimeric forms is also a potent chemoattractant for monocytes. Preliminary
metabolic labeling studies indicate that baboon SMC synthesize and secrete
non-mitogenic, monomeric PDGF-like proteins of MW 100 kD and 12 kD. It is
possible that SMC-CF and PDGF-like protein are related. The aim of these
studies is to determine the primary amino acid sequence of SMC-CF, by
determining the nucleotide sequencing of SMC-CF cDNA and compare it with
the published sequence of PDGF and other proteins for homology. A
polyclonal antiserum to SMC-CF will be developed for use in determining
structural similarity between SMC-CF and PDGF and other chemoattractants.
In addition, antibodies to PDGF and PDGF-related peptides provided by Drs.
Antoniades and Graves will be used. Receptor studies will be carried out
to characterize the binding of SMC-CF to monocytes. The functional
similarity between SMC-CF, PDGF and other chemoattractants will be
determined by competition for receptor sites. The intracellular processing
pathways of both SMC-CF and PDGF-like proteins will be established in the
SMC utilizing immunoprecipitation techniques. The influence of SMC
phenotype on SMC-CF secretion, c-sis expression and the synthesis of
PDGF-like proteins will also be examined. These proposed studies will
provide basic biologic insights into the mechanism whereby SMC might
regulate monocyte recruitment to the intima in atherogenesis.
StatusFinished
Effective start/end date4/1/877/31/90

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

ASJC

  • Medicine(all)

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