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Angiogenesis is the sprouting and branching of new vasculature from existing vessels. Endothelial cell heterogeneity within the neovasculature gives rise to distinct phenotypes such as tip and stalk cells which act in vessel guidance and stabilization. Cells that populate the new vessel can be derived from progenitor differentiation or by recruitment. Angiogenesis provides circulatory support to developing and ischemic tissues. It is a critical process during embryonic development, tissue morphogenesis, pregnancy, wound healing, and tumor development.

Angiogenic Factors and Receptors

Angiogenic factors are secreted by many cell types and can be tethered to the extracellular matrix until they are proteolytically released. These factors bind to receptors on vascular endothelial and smooth muscle cells and control cell proliferation, survival, adhesion, and directed migration.

VEGF (vascular endothelial growth factor) is an essential angiogenesis inducer and also regulates the activity of other angiogenic factors. The VEGF family includes multiple isoforms of VEGF-A as well as VEGF-B, -C, and -D, and PlGF, -2, -3, and -4. These proteins bind and induce signaling through VEGFR1/Flt-1, VEGFR2/KDR/Flk-1, and VEGFR3/Flt-4.

Angiopoietin family proteins regulate angiogenesis through the Tie-1 and Tie-2 receptors. They’re critical for endothelial cell differentiation, blood vessel stabilization and integrity, and pericyte recruitment. The structurally related Angiopoietin-like proteins also regulate angiogenesis through LILR/CD85 family receptors.

Many other proteins regulate angiogenesis in addition to VEGF and Angiopoietin. In some cases they are released during inflammation and contribute to wound healing by promoting cell proliferation and increasing the blood supply for tissue regeneration.

Angiogenic Factors and Receptors

Multianalyte Immunoassays

These assay platforms let you detect many proteins in one experiment. They cover the VEGF and Angiopoietin families as well as the FGF, Notch, Wnt families, and more. These assays are optimized to detect analytes with high sensitivity, low background, and minimal cross-reactivity.

Activity Assays

Our in vivo and in vitro Angiogenesis Assay Kits include all necessary reagents and are optimized for the straightforward and reproducible study of angiogenic function.

Cell Adhesion

Cell surface adhesion proteins mediate the interaction of adjacent cells with each other and with the extracellular matrix (ECM). Adhesion is required to maintain endothelial barrier integrity, vascular wall strength, and the anchoring of vessels within the local tissue. The breakdown of adhesive contacts and the ECM are important for cell migration and neovasculature extension.

Integrin proteins are composed of alpha and beta chains which combine to form heterodimers. The binding of Integrins to ECM molecules triggers intracellular signaling that regulates cytoskeletal rearrangements, cell attachment, and motility.

Cadherins are calcium-dependent adhesion proteins that bind homotypically and with other Cadherins. VE-Cadherin plays a key role in stabilizing vascular sprouts during angiogenesis.

Immunoglobulin superfamily adhesion molecules, particularly CD31/PE-CAM, ICAM-1/CD54, ICAM-2/CD102, JAM-A, JAM-B/VE-JAM, JAM-C, and VCAM-1/CD106, also play critical roles during angiogenesis.

Adhesion contacts with the extracellular matrix and the ECM structure itself are disrupted by matrix metalloproteases (MMPs and ADAMs) which may be present in complex with endogenous tissue inhibitors of metalloproteases (TIMPs). Proteolytic activity is required for cell detachment and migration during angiogenesis.

Cell Adhesion with Endothelial Cell-Endothelial Cell Interactions

Multianalyte Immunoassays

These assay platforms let you detect many proteins in one experiment, including soluble forms of many transmembrane adhesion proteins. They are optimized to detect analytes with high sensitivity, low background, and minimal cross-reactivity.

Vessel Guidance

Effective angiogenesis requires the guidance of neovasculature underserved tissue. Vessel guidance relies on both attractive and repulsive signals that alter the migration path taken by vessel sprouts. Guidance cues are provided by secreted molecules that trigger responses through cell surface receptors on vascular endothelial tip cells.

The interaction of Ephrin-B2 with EphB4 induces forward and reverse signaling that regulates vessel migration during angiogenesis and lymphangiogenesis. These proteins belong to the families of cell surface Ephrin proteins and Eph receptor tyrosine kinases.

Semaphorins are expressed as either transmembrane or secreted proteins and bind to transmembrane Plexin proteins. Interactions between binding partners mediates cell-cell adhesion and triggers signaling to regulate cell migration during angiogenesis.

Slit, ROBO, and Netrin proteins are expressed on or secreted by vascular cells and provide guidance cues involving migration, adhesion, and stabilization.

Effective Angiogenesis Blood Vessel Guidance

Additional Resources

"Chemokine Signaling Pathway"
This interactive pathway covers intracellular signaling downstream of C, CC, CXC, and CX3C chemokine receptors.

"FGF Signaling Pathway"
This interactive pathway covers intracellular signaling downstream of FGF receptors.

"Immunology Pathways"
This collection of interactive pathways covers intracellular signaling downstream of many cytokine receptors.

"Notch Signaling Pathway" 
This interactive pathway includes non-canonical signaling, pre-processing, and NICD translocation.

"VEGF-VEGFR2 Signaling Pathway" 
This interactive pathway covers intracellular signaling important for many vascular functions.

"Angiogenesis in Cancer Poster" 
This poster covers physiological angiogenesis and therapeutic targets for tumor vascularization.

"Atherosclerosis Disease Progression Poster" 
This poster covers healthy vascular function, endothelial damage, plaque progression, and plaque rupture.

"ProteinSimple® Analytical Instrumentation" 
Meet our protein characterization problem solvers – Simple Western™, Maurice, Simple Plex™, Single-Cell Western, MFI™ Systems, and FluorChem™ Systems.

"RNAscope® and BaseScope™ Assays" 
Revolutionary ISH assays capture gene expression in situ at single cell level in intact tissue.

"Bioprocessing: From Start to Finish" 
Instruments, GMP reagents, and services for clone selection through final product characterization.

"Cell and Gene Therapy Solutions" 
Pioneering tools to simplify your workflow – cell separation, cell culture, and quality control.

"GMP Grade Proteins" 
Cytokines and growth factors for ancillary use in preclinical to clinical studies.