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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2009;29:630.)
© 2009 American Heart Association, Inc.

Brief Reviews

Endothelial-Mural Cell Signaling in Vascular Development and Angiogenesis

Konstantin Gaengel; Guillem Genové; Annika Armulik; Christer Betsholtz

From the Vascular Biology Laboratory, Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.

Correspondence to Christer Betsholtz, Vascular Biology Laboratory, Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Scheeles väg 2, SE 171 77, Stockholm, Sweden. E-mail christer.betsholtz{at}ki.se

Series Editor: Mark Majesky PhD

Mural cells are essential components of blood vessels and are necessary for normal development, homeostasis, and organ function. Alterations in mural cell density or the stable attachment of mural cells to the endothelium is associated with several human diseases such as diabetic retinopathy, venous malformation, and hereditary stroke. In addition mural cells are implicated in regulating tumor growth and have thus been suggested as potential antiangiogenic targets in tumor therapy. In recent years our knowledge of mural cell function and endothelial-mural cell signaling has increased dramatically, and we now begin to understand the mechanistic basis of the key signaling pathways involved. This is mainly thanks to sophisticated in vivo experiments using a broad repertoire of genetic technologies. In this review, we summarize the five currently best understood signaling pathways implicated in mural cell biology. We discuss PDGFB/PDGFRβ- dependent pericyte recruitment, as well as the role of angiopoietins and Tie receptors in vascular maturation. In addition, we highlight the effects of sphingosine-1-phosphate signaling on adherens junction assembly and vascular stability, as well as the role of TGF-β-signaling in mural cell differentiation. We further reflect recent data suggesting an important function for Notch3 signaling in mural cell maturation.

Mural cells are essential components of blood vessels, and their defective association with the endothelium is associated with several human diseases. Here we summarize the key signaling pathways in mural cell biology with a focus on PDGFB/PDGFRβ, Angiopoietins, and Tie receptors, sphingosine-1-phosphate, TGFβ, and Notch signaling.

Key Words: pericyte • PDGF • angiopoietin • sphingosine-1-phosphate • TGF-β

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