Circulation, Vol 90, 677-685, Copyright © 1994 by American Heart Association
XM Zhao, TK Yeoh, WH Frist, DL Porterfield and GG Miller
BACKGROUND: Further understanding of cardiac allograft vasculopathy (CAV)
is needed to improve long-term survival after cardiac transplantation. The
diffuse hyperplasia of coronary intima characteristic of CAV suggests that
growth factors may play a role in the development of CAV. Fibroblast growth
factor (FGF) and platelet- derived growth factor (PDGF) are potent mitogens
for smooth muscle cells (SMCs), and PDGF is an important cofactor in the
pathogenesis of native coronary atherosclerosis. METHODS AND RESULTS:
Reverse transcriptase/polymerase chain reaction (RT/PCR), in situ
hybridization, and immunohistochemistry were used to determine whether
transplantation results in increased cardiac expression of acidic (a) FGF,
basic (b) FGF, and PDGF-A and -B chains. Sixty-eight myocardial biopsies
from 36 heart transplant recipients and 7 normal hearts were analyzed by
PCR. aFGF mRNA was present in 54 of 61 allograft biopsies and was not found
in any normal heart. In situ hybridization and immunohistochemistry
demonstrated diffuse, intense expression of a FGF mRNA and protein in
allograft biopsies, predominantly in myocytes and vascular walls. Only
scattered aFGF expression was observed in normal hearts. mRNA for the
full-length isoform of PDGF-A chain was found in 43 of 61 allograft
biopsies and was not detected in any normal heart. In situ hybridization
and immunohistochemistry confirmed that full- length PDGF-A chain mRNA and
PDGF protein were present in myocytes and vascular walls. CONCLUSIONS:
Expression of aFGF and PDGF-A chain is significantly increased in cardiac
allografts. Cardiac myocytes and vascular walls are the predominant sources
of aFGF and PDGF. Diffuse expression of these growth factors in cardiac
allografts may be important in the pathogenesis of CAV.
ARTICLES
Induction of acidic fibroblast growth factor and full-length platelet- derived growth factor expression in human cardiac allografts. Analysis by PCR, in situ hybridization, and immunohistochemistry
Vanderbilt Transplant Center, Nashville, Tenn.
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