Vasohibin-1

Mechanism of Action

• Secreted by endothelium in response to VEGF/FGF, creating an auto-regulatory brake on vessel sprouting
• Detyrosinates alpha-tubulin via carboxypeptidase activity, stabilizing microtubule arrays and reducing endothelial motility
• Reduces endothelial cell migration, proliferation, and tube formation in Matrigel assays
• Downregulates eNOS expression, limiting nitric oxide-driven vasodilation in newly forming vessels
• Synergizes with thrombospondin-1 and endostatin in multi-target anti-angiogenic strategies

Research Findings

• Elevated VASH1 correlates with better prognosis in colorectal, gastric, and renal cell carcinomas
• Recombinant VASH1 protein suppressed tumor growth in mouse xenograft models at 1-10 mg/kg dosing
• VASH1 expression is reduced in wet AMD choroidal neovascularization, suggesting therapeutic potential
• Loss of VASH1 function (VASH1 knockout mice) leads to exaggerated angiogenic response to injury
• VASH1/SVBP complex identified as responsible for alpha-tubulin detyrosination in neurons and endothelium

Research Protocols

• In vitro: recombinant rhVASH1 at 100-500 ng/mL in endothelial tube formation or migration assays
• In vivo mouse tumor models: 1-5 mg/kg IV or peritumoral injection of purified VASH1 protein
• AAV-VASH1 gene delivery in ocular neovascularization models (intravitreal injection)
• No approved clinical protocols; research-grade recombinant protein only

Interactions

• SVBP (small vasohibin-binding protein): obligate partner for secretion and enzymatic function
• Bevacizumab/VEGF inhibitors: additive anti-angiogenic effect in preclinical models
• Thrombospondin-1: synergistic inhibition of endothelial tube formation

Safety Profile

Investigational research protein. No human dosing data. Recombinant VASH1 generally well tolerated in rodent studies at tested doses. No commercial therapeutic product approved.

Legal & Regulatory

Research use only