Background-Endothelial receptor tyrosine kinases include 3 members of the v
ascular endothelial growth factor receptor (VEGFR) family and 2 members of
the angiopoietin receptor (Tie) family. In addition, the VEGF(165) isoform
binds to neuropilin-1 (NP-1), a receptor for collapsins/semaphorins. The im
portance of these receptors for vasculogenesis and angiogenesis has been sh
own in gene-targeted mice, but so far, little is known about their exact ex
pression patterns in the human vasculature.
Methods and Results-Frozen sections of human fetal heart were stained immun
ohistochemically with receptor-specific monoclonal (VEGFR, Tie) or polyclon
al (NP-1) antibodies. The following patterns were observed: The endocardium
was positive for VEGFR-1, VEGFR-2, NP-I, Tie-1, and Tie-2 but negative for
VECFR-3. The coronary vessels were positive for Tie-1, Tie-2, VEGFR-1, and
NP-1 and negative for VEGFR-2 and VEGFR-3. Myocardial capillaries and epic
ardial blood vessels stained for VEGFR-1, VEGFR-2, NP-1, and Tie-1; myocard
ial capillaries and epicardial veins weakly for Tie-2; and epicardial lymph
atic vessels for VEGFR-2 and VEGFR-3, weakly for Tie-1 and Tie-2, but not f
or VEGFR-1 or NP-1.
Conclusions-The results demonstrate differential expression of the endothel
ial growth factor receptors in distinct types of vessels in the human heart
. This information is useful for the understanding of their roles in physio
logical and pathological processes and for their diagnostic and therapeutic
application in cardiovascular medicine.