Angiogenesis signaling

Neovascularization couples hypoxia-inducible transcription, VEGF–VEGFR–driven endothelial proliferation/migration, Notch/DLL4 tip–stalk fate decisions, and Tie2–angiopoietin control of maturation and pericyte coverage. Pathological vessels in cancer, chronic inflammation, or ischemia often show high permeability, structural immaturity, and therapy resistance—interpret with multiplex readouts.

1. Key targets

Core nodes

  • VEGFA / VEGFC & KDR / FLT1

    Ligand–receptor tyrosine kinase axis; sprouting, survival, permeability (context-dependent).

  • TEK (Tie2) / ANGPT1 / ANGPT2

    Vessel maturation/stability; ANGPT2 often destabilizes in tumor settings.

  • NOTCH1 / DLL4 / JAG1

    DLL4-high tip cells and lateral inhibition; branching patterning.

Hypoxia & transcription

  • HIF1A / EPAS1 (HIF2A); PHD–VHL regulation
  • Downstream clusters (VEGFA, GLUT1, LDHA—model-dependent)

Endothelial phenotype & matrix

  • CDH5 (VE-cadherin), CD31, Endoglin (ENG)
  • MMP2/9, integrins, basement-membrane collagen remodeling
  • PDGFRB, NG2 (CSPG4)—pericyte coverage

2. Suggested experimental readouts

Pair structural readouts (pericytes, basement membrane) with functional assays (perfusion, permeability); for phospho targets, include totals and dose/time controls.

  • CD31 / CD34 / IB4 with sprout metrics (organoid/aortic ring models)
  • p-ERK, p-AKT; total KDR/FLT1 (phospho sites per clone)
  • DLL4, NOTCH1 enrichment at tips; Hey1/HEY2 transcriptional readouts
  • α-SMA / PDGFRB / NG2 with CD31—pericyte coverage index
  • Hypoxia probes or HIF1A nuclear localization (fixation-sensitive)
  • Tubulogenesis assays (batch-to-batch matrix/serum variability)

3. VEGF axis vs Tie2–angiopoietin axis

AxisKey ligand–receptorTypical rolesPractical notes
VEGFVEGFA/C → KDR / FLT1Sprouting, migration, survival, permeabilityTKIs vs neutralizing antibodies differ mechanistically.
Angpt–Tie2ANGPT1/2 → TEK (Tie2)Maturation/stability; tumor contexts remodel mural attachmentPair with VEGF for normalization vs resistance narratives.

4. Tumor vessels: phenotypes, normalization & resistance

  • Immature structure: Discontinuous basement membrane, low pericyte coverage—often high leakiness and interstitial pressure.
  • Normalization window: Transient perfusion/delivery improvements; timing is tumor- and regimen-specific.
  • Compensatory pathways: FGF, Angpt, Notch shifts, or myeloid/stromal reprogramming can drive revascularization.

Angiogenesis-related antibodies (curated)

Loading…

5. Product lines & on-site search

Primary & phospho antibodies

VEGFA, KDR, FLT1, Tie2, DLL4, Notch1, CD31, CDH5, Endoglin, HIF1A, MMP2/9, PDGFRB—WB/IHC/IF/FC as applicable.

Recombinant proteins / cytokines

VEGF165, PlGF, Angpt1/2 for co-culture/stimulation—match species and titrate controls.

Functional reagents & quantification

Neutralizing anti-VEGF, soluble traps, species-matched VEGFA ELISAs—follow datasheets and ethics.

6. Inhibitors & tool compounds (summary)

For research use; follow lab SOP and datasheets. Clinical biologics (e.g., bevacizumab-class) depend on institutional access.

Sunitinib

Multi-kinase inhibitor; VEGFR/PDGFR/c-KIT (model-dependent).

Sorafenib

RAF/VEGFR multi-target; common control arm.

Axitinib

VEGF-axis-preferring TKI; common in vascular phenotyping.

Regorafenib

Broader VEGFR/FGFR profile; watch off-target toxicity.

Lenvatinib

VEGFR1–3 / FGFR / PDGFR, etc.; combine studies need monotherapy controls.

Cabozantinib

MET/VEGFR2, etc.; invasion–angiogenesis crosstalk studies.

Apatinib

VEGFR2-selective small molecule (regional approval varies).

DAPT / RO4929097

γ-secretase / Notch tools; alters tip–stalk allocation.

7. Pathway schematic

Angiogenesis (simplified schematic)
Angiogenesis pathway schematic
Legend
  1. Hypoxia–HIF drives VEGF transcriptional output
  2. VEGFR→MAPK/PI3K and migratory cytoskeleton programs
  3. Tie2–Angpt regulates stability and mural attachment
  4. Notch/DLL4 with matrix remodeling shapes branching

8. Pathway biology overview

Physiologic angiogenesis is tightly spatiotemporally controlled during development and repair; pathology couples pro-angiogenic cues, matrix mechanics, and immune cells to reprogram endothelial metabolism and heterogeneity.

  • Lymphangiogenesis (VEGFC/D–FLT4) may parallel blood vessels—use distinct markers
  • Organ specificity: BBB vs liver sinusoids differ substantially

9. Related pathways on this site

TGF-β/Smad (Endoglin crosstalk)RTKs (including VEGFR)Notch (tip/stalk)MAPK/ERKPI3K/Akt/mTORNF-κBJAK-STATMetabolism

10. External databases & modification resources

11. References

VEGF & angiogenesis mechanisms

  • • Ferrara N, Kerbel RS. (2005). Nature. 438(7070):967-74.
  • • Carmeliet P, Jain RK. (2011). Nature. 473(7347):298-307.

Tip cells & Notch

  • • Hellström M, et al. (2007). Nature. 445(7129):776-80.
  • • Phng LK, Gerhardt H. (2009). J Cell Sci. 122(Pt 17):3151-9.