Vascular Morphogenesis and Angiogenic Mechanisms

Vascular morphogenesis encompasses the formation, patterning and maturation of blood vessels through coordinated cellular, molecular and mechanical processes. It comprises vasculogenesis, whereby endothelial progenitors assemble de novo, and angiogenesis, the sprouting and remodelling of existing networks. Central to these events are growth factor–receptor interactions, notably VEGF–VEGFR and Notch signalling, which regulate the selection and behaviour of motile tip cells and proliferative stalk cells. Concomitant remodelling of the extracellular matrix via integrins and metalloproteinases supports directed endothelial migration, lumen formation and stabilisation. Small GTPases orchestrate cytoskeletal dynamics that underpin vacuole trafficking and membrane polarity during lumenogenesis. Recruitment of pericytes and deposition of basement membrane confer vessel integrity and control permeability. Insights into hydrostatic pressure–driven cell migration and aquaporin channels have revealed alternative mechanisms augmenting actin-mediated motility. Understanding these interlinked processes is vital for addressing pathological angiogenesis in cancer, ischaemic disease and advancing tissue-engineering applications.

Research from Nature Portfolio

Recent studies have delineated the role of integrin α3β1 in tumour-associated endothelial cells, demonstrating that its overexpression promotes nascent lumen formation via calcium-dependent macropinocytosis and lysosomal exocytosis, thereby enhancing vessel assembly within glioblastoma. Another investigation has characterised how differential expression of integrins αv and α5 influences cellular responses to matrix cues, revealing distinct pathways by which these receptors regulate proliferation, survival and morphogenetic signalling that may parallel endothelial behaviours during vessel formation.

Vascular Morphogenesis and Angiogenic Mechanisms publication trend

The graph below shows the total number of articles in vascular morphogenesis and angiogenic mechanisms across all publications each year (not limited to Nature Index journals).

Technical terms

Vasculogenesis: The de novo assembly of endothelial progenitors into primitive vascular networks.

Sprouting angiogenesis: The branching of new capillaries from existing vessels, driven by specialised tip and stalk cell dynamics.

Lumenogenesis: The process by which intracellular vacuoles and membrane trafficking establish a central vessel lumen.

Pericyte: A mural cell that associates with endothelial tubes to stabilise and mature capillaries.

Integrin α3β1: A cell-matrix adhesion receptor critical for endothelial lumen formation and tube morphogenesis.

References

1. Combined forces of hydrostatic pressure and actin polymerization drive endothelial tip cell migration and sprouting angiogenesis. eLife (2025).
2. Enhancing human capillary tube network assembly and maturation through upregulated expression of pericyte-derived TIMP-3. Frontiers in Cell and Developmental Biology (2024).
3. SH2 domain protein E and ABL signaling regulate blood vessel size. PLOS Genetics (2024).
4. Integrin α3β1 promotes vessel formation of glioblastoma-associated endothelial cells through calcium-mediated macropinocytosis and lysosomal exocytosis. Nature Communications (2022).
5. Control of endothelial tubulogenesis by Rab and Ral GTPases, and apical targeting of caveolin-1-labeled vacuoles. PLOS ONE (2020).