The angiogenic growth of blood-vessel capillaries involves sprouting and branching processes that are, in part, controlled by Notch signalling. Gradients of matrix-bound vascular endothelial growth factor A (VEGFA) and other navigational cues are recognized by specialized endothelial tip cells at the distal end of each sprout.
The recruitment of bone-marrow-derived monocytic cells to the perivascular space is an important process in adult angiogenesis.
The transcription factor prospero-related homeobox-1 (PROX1) is an important regulator of lymphatic endothelial cell differentiation. Sprouting, migration and proliferation of lymphatic endothelial cells is regulated by VEGFC and the VEGF receptor-3 (VEGFR3).
Arteriovenous identity is controlled by haemodynamic factors and, at least in some settings, genetic programmes. Such programmes involve the expression of Notch-pathway molecules in arterial endothelial cells whereas venous expression of these genes is actively suppressed by COUP-TFII, a member of the orphan nuclear receptor superfamily.
Pericytes and vascular smooth-muscle cells stabilize blood vessels and their incorporation into the vessel wall is an important part of the maturation programme.
Defective lymphangiogenic growth and compromised lymphatic endothelial cell identity appear to be interdependent. Known genes that are required for the differentiation of terminal lymphatics and collecting lymphatics as well as the formation of valves are forkhead box-c2 (FOXC2), angiopoietin-2 (ANG2) and ephrin-B2 (EFNB2).
Blood vessels and lymphatic vessels form extensive networks that are essential for the transport of fluids, gases, macromolecules and cells within the large and complex bodies of vertebrates. Both of these vascular structures are lined with endothelial cells that integrate functionally into different organs, acquire tissue-specific specialization and retain plasticity; thereby, they permit growth during tissue repair or in disease settings. The angiogenic growth of blood vessels and lymphatic vessels coordinates several biological processes such as cell proliferation, guided migration, differentiation and cell–cell communication.
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The authors thank several colleagues for collaboration and apologise to those whose work could not be cited owing to lack of space. Work in the authors' laboratories is supported by grants from Finnish Cancer Organizations, Sigrid Juselius Foundation, Academy of Finland, Novo Nordisk Foundation, European Union, National Institutes of Health, Louis Jeantet Foundation and Helsinki University Central Hospital.
The authors declare no competing financial interests.
Mesoderm-derived endothelial precursor cells that are not fully differentiated and retain some stem-cell properties.
The cell layer in the vertebrate embryo that differentiates into mesenchyme, connective tissue, bone, muscle, the cardiovascular system and blood cells.
Mesoderm-derived embryonic connective tissue that generates bone, cartilage, fibroblasts, smooth muscle and other cell types.
Mesenchyme-derived cells that cover blood vessels and make direct contact with endothelial cells through numerous long processes. Pericyte–endothelial interactions involve adhesion molecules and ion channels, and stabilize the endothelium.
Slender cellular processes that extend from the front of migrating cells, attach to the surrounding matrix and help to move cells forward.
- Mural cells
Cells of the outer vessel wall: pericytes and vascular smooth-muscle cells.
- Axonal growth cones
Dynamic guidance structures at the distal end of growing nerve fibres that direct fibres to their appropriate targets and thereby promote the correct 'wiring' of the nervous system.
Uptake of extracellular liquid into cells in the form of membrane-coated vesicles.
- Vascular smooth-muscle cells
Specialized smooth-muscle cells that form the outer layer of arteries, arterioles and larger veins. They provide blood vessels with mechanical stability that is due to their contractile properties and the deposition of matrix and elastic fibres.
Specialized, highly branched epithelial cell in the filtering units (glomeruli) of the kidney. Numerous podocyte foot processes cover the glomerular capillary basement membrane and thereby form a size-selective filtration barrier that is permeable to water, salts and glucose but retains macromolecules in the bloodstream.
Harmful interstitial liquid accumulation that is due to insufficient lymphatic drainage.
- Neural crest cells
Ectodermal cells that delaminate from the neural tube in vertebrate embryos, migrate to various locations and contribute to different body structures such as the peripheral nervous system, bone and cartilage, skeletal and smooth muscle, or pigment cells in the skin (melanocytes).
- Vascular stem cells
Stem cells that can differentiate into endothelial or mural cells in the blood vessel wall.
Precursor cells that can differentiate into endothelial and haematopoietic cells.
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Adams, R., Alitalo, K. Molecular regulation of angiogenesis and lymphangiogenesis. Nat Rev Mol Cell Biol 8, 464–478 (2007). https://doi.org/10.1038/nrm2183
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Mechanical loading of intraluminal pressure mediates wound angiogenesis by regulating the TOCA family of F-BAR proteins
Nature Communications (2022)
Med23 supports angiogenesis and maintains vascular integrity through negative regulation of angiopoietin2 expression
Communications Biology (2022)