The Vascular Endothelial Growth Factor (VEGF) family is a group of particular endothelial growth factors intimately associated with angiogenesis. These factors promote increased vascular permeability, extracellular matrix degeneration, vascular endothelial cell migration and proliferation, and are capable of stimulating angiogenesis and increasing the permeability of existing vessels. As such, they play a pivotal role in normal vascular development and wound healing. The VEGF family comprises VEGFA, VEGFB, VEGFC, VEGFD, VEGFE, and PLGF ^[1]. Of these, VEGFA is the most commonly targeted in research related to neovascular ophthalmic diseases due to its crucial role in the proliferation, migration, and formation of endothelial cell microvessels ^[2]. Overexpression of VEGFA in the eye can result in abnormal vascular growth and leakage, leading to various ophthalmic diseases such as Age-Related Macular Degeneration (AMD), Diabetic Retinopathy (DR), and corneal neovascularization ^[2-3]. The progression of solid tumors depends on vascularization and angiogenesis within malignant tissues, with VEGFA playing a crucial role among various pro-angiogenic factors. The VEGFA gene is upregulated in many known tumors, correlating with tumor staging and progression. Blocking VEGFA may lead to vascular network regression, thereby inhibiting tumor growth ^[4]. Thus, VEGFA is an important target for anti-angiogenic cancer therapies.

Angiopoietin-2 (ANG2/ANGPT2), encoded by the ANGPT2 gene, is a secreted glycoprotein of the angiopoietin family predominantly expressed in vascular endothelial cells and stored in Weibel-Palade bodies for rapid release. ANGPT2 regulates vascular biology in a context-dependent manner by binding to the Tie2 tyrosine kinase receptor, playing pivotal roles in angiogenesis and vascular remodeling ^[5]. Its molecular structure includes a coiled-coil domain facilitating oligomerization and a fibrinogen-like domain critical for receptor binding. Functionally, ANGPT2 acts as a partial Tie2 receptor antagonist to Angiopoietin-1 (ANG1). Through competitive inhibition of Tie2 signaling, ANGPT2 disrupts vascular endothelial homeostasis, inducing increased vascular permeability and structural plasticity. In synergy with vascular endothelial growth factor (VEGF), ANGPT2 drives angiogenic sprouting and pathological neovascularization. Conversely, under conditions of low or absent VEGF, it mediates vascular regression ^[6-7]. ANGPT2 plays a central pathological role in vascular proliferative diseases such as tumor angiogenesis, diabetic retinopathy, and age-related macular degeneration. Endothelial cell activation and inflammatory responses mediated by ANGPT2 also contribute to the pathogenesis of inflammatory conditions including sepsis and rheumatoid arthritis ^[8]. Therapeutic strategies targeting ANGPT2 include monoclonal antibodies (e.g., Nesvacumab) and peptide-Fc fusion proteins (e.g., Trebananib), often combined with VEGF inhibitors to enhance anti-angiogenic efficacy ^[9-10]. Current research efforts are focused on optimizing ANGPT2/VEGF dual-target inhibition strategies and developing biomarkers, aiming to improve clinical outcomes in tumors and ocular vascular diseases and validate its translational value as a therapeutic target in vascular and inflammatory diseases ^[11-12].

B6-hVEGFA/hANGPT2 mice are VEGFA and ANGPT2 double humanized mouse models obtained by mating VEGFA humanized mouse models (Catalog No. C001555) with ANGPT2 humanized mouse models (Catalog No. C001615). B6-hVEGFA/hANGPT2 mice express human VEGFA and ANGPT2 genomic sequences under the control of mouse promoters. This model is capable of reproducing human VEGFA and ANGPT2 and is a valuable tool for studying cancer, vascular diseases and autoimmune disorders. In addition, this model also provides a powerful preclinical research platform for evaluating the efficacy and mechanism of therapeutic drugs targeting VEGFA and ANGPT2.