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(Circulation. 1999;100:583-586.)
© 1999 American Heart Association, Inc.

Brief Rapid Communication

Endothelial Growth Factor Receptors in Human Fetal Heart

Taina A. Partanen, MD; Taija Makinen, MSc; Johanna Arola, MD, PhD; Toshio Suda, MD, PhD; Herbert A. Weich, MD, PhD; Kari Alitalo, MD, PhD

From the Molecular/Cancer Biology Laboratory (T.A.P., T.M., K.A.) and Department of Pathology (J.A.), Haartman Institute, University of Helsinki, Finland; the Department of Cell Differentiation (T.S.), IMEG, Kumamoto University School of Medicine, Japan; and the Department of Gene Regulation and Differentiation (H.A.W.), Division of Molecular Biotechnology, National Research Center for Biotechnology (GBF), Germany.

Correspondence to Dr Kari Alitalo, Molecular/Cancer Biology Laboratory, Haartman Institute, POB. 21 (Haartmaninkatu 3), University of Helsinki, FIN-00014 Helsinki, Finland. E-mail kari.alitalo{at}helsinki.fi

Background—Endothelial receptor tyrosine kinases include 3 members of the vascular endothelial growth factor receptor (VEGFR) family and 2 members of the angiopoietin receptor (Tie) family. In addition, the VEGF₁₆₅ isoform binds to neuropilin-1 (NP-1), a receptor for collapsins/semaphorins. The importance of these receptors for vasculogenesis and angiogenesis has been shown in gene-targeted mice, but so far, little is known about their exact expression patterns in the human vasculature.

Methods and Results—Frozen sections of human fetal heart were stained immunohistochemically with receptor-specific monoclonal (VEGFR, Tie) or polyclonal (NP-1) antibodies. The following patterns were observed: The endocardium was positive for VEGFR-1, VEGFR-2, NP-1, Tie-1, and Tie-2 but negative for VEGFR-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 epicardial blood vessels stained for VEGFR-1, VEGFR-2, NP-1, and Tie-1; myocardial capillaries and epicardial veins weakly for Tie-2; and epicardial lymphatic vessels for VEGFR-2 and VEGFR-3, weakly for Tie-1 and Tie-2, but not for VEGFR-1 or NP-1.

Conclusions—The results demonstrate differential expression of the endothelial growth factor receptors in distinct types of vessels in the human heart. This information is useful for the understanding of their roles in physiological and pathological processes and for their diagnostic and therapeutic application in cardiovascular medicine.

Key Words: angiogenesis • endothelium • endocardium • myocardium • growth substances

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