Mechanism of Action
Angiogenesis Negative Feedback
VASH1 is induced in endothelial cells by VEGF, FGF, and other pro-angiogenic factors, then secreted to inhibit further sprouting. It reduces endothelial cell migration and proliferation while promoting endothelial stress resistance and quiescence. VASH1 forms a complex with Small Vasohibin Binding Protein (SVBP) which is required for secretion and catalytic activity.
Tubulin Carboxypeptidase Activity
VASH1 was identified in 2017 as the long-sought tubulin carboxypeptidase (TTCP), the enzyme that removes the C-terminal tyrosine from alpha-tubulin. Alpha-tubulin detyrosination is a key post-translational modification that alters microtubule dynamics, motor protein interactions, and centriole stability. This discovery connected VASH1 to cancer metastasis, neuronal differentiation, and cardiac hypertrophy through microtubule regulation.
Research Summary
Tumor Angiogenesis Suppression
PreclinicalVASH1 overexpression or recombinant protein delivery reduces tumor vascularization and growth in mouse models of breast, colon, and pancreatic cancer. VASH1 deficiency leads to excessive tumor angiogenesis, while restoration suppresses tumor growth. Gene therapy vectors delivering VASH1 have been studied as potential antiangiogenic cancer therapeutics.
Tubulin Detyrosination in Disease
PreclinicalElevated VASH1/TTCP activity with increased alpha-tubulin detyrosination is found in heart failure and aggressive cancers. VASH1 inhibitors reduce cardiac detyrosination and improve cardiac function in pressure overload models. VASH1 inhibition also reduces metastatic capacity of cancer cells that rely on detyrosinated microtubule networks for migration. Small molecule VASH1/SVBP inhibitors are in early development.
Calculate your Vasohibin dose Vial strength, BAC water, exact syringe draw in IU. Free, no signup. Open Calc →
Research Protocols
| Goal | Dose | Frequency | Route |
|---|---|---|---|
| Angiogenesis inhibition (in vivo) | 10-50 ug/kg (recombinant protein) | Multiple injections | IV / SC (research) |
| Tubulin assays (in vitro) | Nanomolar enzyme concentrations | Single treatment | Direct application |
No human research protocols. All models are preclinical.
Interactions
Safety Profile
As an endogenous protein, VASH1 is expected to have favorable immunogenicity profile. Long-term angiogenesis suppression may affect wound healing and reproductive function. The tubulin detyrosination inhibition pathway presents separate mechanistic concerns for neuronal and cardiac function. No human clinical data available.
References
- [1]Sato Y, et al. (2001). Identification of a new type of angiogenesis inhibitor, vasohibin. J Clin Invest, 107(9), 1167-1174.
- [2]Aillaud C, et al. (2017). Vasohibins/SVBP are tubulin carboxypeptidases (TCPs) that regulate neuron differentiation. Science, 358(6369), 1448-1453.