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.

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Angiogenic Factors

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.

structure of R&D Systems human VEGF protein

Multianalyte Immunoassays for Adhesion Proteins

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 for Angiogenesis

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.

molecules in angiogenesis ECM and cell adhesion

Neovasculature Vessel Guidance

Effective angiogenesis requires the guidance of neovasculature to 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.

molecules in neovascular vessel guidance
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