Growth factor signaling pathways in vascular development

Abstract

Recent research on the formation and maintenance of the vasculature in the embryo and in the adult has provided a greater understanding of the cellular signals involved in these processes. With this understanding comes the potential means of controlling vascularization in pathological situations such as tumorigenesis and wounding. For the purpose of this review, we will discuss the key receptor tyrosine kinases involved in vascular function and the molecules which relay signals downstream of receptor activation. The receptor tyrosine kinases discussed include the vascular endothelial cell growth factor receptors, Eph receptors, Tie1, and Tie2, all of which are expressed on vascular endothelial cells. We also discuss the roles of the platelet derived growth factor receptors which are expressed on vascular smooth muscle cells. While all of these receptor tyrosine kinases activate many similar effector molecules, some of the signals initiated appear to be distinct. This may explain, at least in part, how different receptor tyrosine kinases expressed in overlapping patterns on the developing vasculature, direct unique biological functions.

Expression of platelet-derived growth factors and their receptors in ovarian clear-cell carcinoma and its putative precursors

“…However, PDGFs including PDGF-BB are natural ligands present in stromal cells such as fibroblasts, and the smooth muscle and endothelium of blood vessels, which constitute the major proportion of the stroma necessary for tumor growth and invasion, and these were constantly positive for PDGF-A and PDGF-B in the present study. 19,20 These observations appear to support the hypothesis that not only an autocrine loop but also a paracrine loop of PDGFRs/PDGFs contributes to tumor progression of clear-cell adenocarcinoma. Although not studied in the present series, PDGF-D, which has been recently cloned, binds PDGFR-b and shows mitogenic properties.…”

“…Fallopian tube epithelium or endothelium of vessels included in the sections served as a built-in-control for all four antibodies, and as a reference for normal expression of the proteins analyzed. 19,20 As negative controls, sections without the primary antibody were used.…”

Nitric oxide modulates murine yolk sac vasculogenesis and rescues glucose induced vasculopathy

“…Loss of many of these molecules leads to vascular dysfunction characterized by enlarged, hyperfused capillaries and embryonic lethality due to cardiovascular defects. Despite the knowledge gained from these studies, the regulatory molecules and signaling events underlying vessel development and patterning remain largely unknown (Darland and D'Amore, 2001;Tallquist et al, 1999). One possible candidate is nitric oxide (NO), a small multifunctional gaseous molecule that acts as a vasoactive agent, signaling molecule and free radical in mammalian Nitric oxide (NO) has been demonstrated to mediate events during ovulation, pregnancy, blastocyst invasion and preimplantation embryogenesis.…”

Notch signaling during vascular development

“…A number of different intercellular signaling pathways have been implicated in the control of these processes. These pathways include the vascular endothelial growth factor pathway, the transforming growth factor-␤ and platelet-derived growth factor pathways, the angiopoietin͞ Tie receptor pathway, and the ephrin͞Eph receptor pathway (2)(3)(4). Recent work has added the Notch signaling pathway to this list.…”

“…These endothelial cells then coalesce and form the primary vascular plexus, a network of homogeneously sized primitive blood vessels. This vascular network is then remodeled by the process of angiogenesis, which involves the sprouting, branching, splitting, and differential growth of vessels in the primary plexus to form the large and small vessels of the mature vascular system (1)(2)(3)(4). During this phase of angiogenic vascular remodeling, supporting cells such as pericytes and smooth muscle cells are recruited to the vessels to provide structural support and stability for the vascular walls.…”