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Molecular regulation of vessel maturation

Abstract

The maturation of nascent vasculature, formed by vasculogenesis or angiogenesis, requires recruitment of mural cells, generation of an extracellular matrix and specialization of the vessel wall for structural support and regulation of vessel function. In addition, the vascular network must be organized so that all the parenchymal cells receive adequate nutrients. All of these processes are orchestrated by physical forces as well as by a constellation of ligands and receptors whose spatio-temporal patterns of expression and concentration are tightly regulated. Inappropriate levels of these physical forces or molecules produce an abnormal vasculature—a hallmark of various pathologies. Normalization of the abnormal vasculature can facilitate drug delivery to tumors and formation of a mature vasculature can help realize the promise of therapeutic angiogenesis and tissue engineering.

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Figure 1: Wall composition of nascent versus mature vessels.

Debbie Maizels

Figure 2: Steps in network formation and maturation during embryonic (physiological) angiogenesis (a) and tumor (pathological) angiogenesis (b).

Debbie Maizels

Figure 3: Vessel normalization and EC–mural cell interactions in tumors growing in dorsal windows in mice.

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Acknowledgements

Due to length limitations, references cited are limited to review articles and Supplementary Table 1 online. The author apologizes to the authors of the original articles not cited. The author thanks R. Jones, P. D'Amore, D. McDonald, and J. Samson, and members of the Steele Lab, especially N. Koike, L. Munn, R. Tong, E. di Tomaso, D. Duda, Y. Boucher, J. Baish, D. Fukumura and B. Stoll, for their invaluable help in preparing this manuscript. The author's work is supported by grants from the National Cancer Institute.

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Jain, R. Molecular regulation of vessel maturation. Nat Med 9, 685–693 (2003). https://doi.org/10.1038/nm0603-685

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