ANGPT1/ANGPT2 Specific Neutra™ Antibody Products

Angiopoietins are a class of growth factors that interact with the tyrosine kinase receptors, Tie1 and Tie2. Among these, angiopoietin-1 (ANGPT1) and angiopoietin-2 (ANGPT2) are the most extensively characterized. ANGPT1 is recognized as a potent angiogenic growth factor that signals through the Tie2 receptor. It is known for its vasculoprotective effects and plays a crucial role in vessel maturation, migration, and cell survival. Whereas ANGPT2 was initially identified as a vascular-disruptive agent with antagonistic properties towards the same receptor. This protein function varies with context, acting as both an agonist and antagonist of TIE2. Elevated levels of ANGPT2 are observed in various inflammatory conditions, where it is implicated in the direct modulation of inflammation-associated signaling pathways.

Angiopoietin-Tie2 Pathways

The Angiopoietin (Angpt)-Tie pathway plays a pivotal role in regulating vascular permeability and pathological vascular remodeling in conditions such as tumor angiogenesis, inflammation and metastasis. The binding of ANGPT1 to the Tie2 receptor results in the phosphorylation of the receptor's intracellular tyrosine split domain, which facilitates endothelial-cell migration and survival, primarily through the PI3K/Akt signaling pathway. Additionally, ANGPT1 signaling robustly activates Rac1, thereby shifting the balance between RhoA and Rac1 in favor of Rac1. Inflammatory stimuli trigger the secretion of ANGPT2 from Weibel-Palade bodies. While ANGPT2 acts as a weak TIE2 agonist under normal conditions dependent on TIE1, it functions as a TIE2 antagonist during inflammation, possibly through inflammation-induced TIE1 ectodomain cleavage. ANGPT2 antagonism activates the FOXO1 pathway, enhancing the expression of FOXO1 target genes such as Angpt2. Conversely, inflammation-induced reduced flow lowers TIE2 levels. Under these circumstances, ANG2 may signal via endothelial integrins, particularly evident in scenarios like choroidal neovascularization in mice.

Fig.1 Diagrammatic representation of the endothelial Angiopoietin (Angpt)/Tie2 network emphasizing core signaling routes.¹

Anti-ANGPT1/ ANGPT2 Antibodies

• Anti-ANGPT1/ANGPT2 Antibody Modulation of Vascular Function in VSMC Akt1 Signaling

Retinal angiogenesis exhibits delayed progression in mice with VSMC-specific Akt1 deficiency (Akt1^ΔSMC), accompanied by impaired endothelial cell proliferation, pericyte recruitment, and vascular smooth muscle cell coverage. Akt1 silencing in VSMCs results in ANGPT1 downregulation and ANGPT2 upregulation. YAP's nuclear localization and transcriptional activity are modulated by Akt1 expression levels. YAP silencing decreases ANGPT2 expression, whereas YAP overexpression yields converse outcomes. Antibodies targeting ANGPT1 and ANGPT2 inhibit endothelial sprouting in wild-type aortic tissues, whereas ANGPT2 antibody and ANGPT1 promote sprouting in aortic tissues from Akt1^ΔSMC mice. Severe hemorrhaging occurs in Akt1^ΔSMC mice, exacerbated under streptozotocin-induced diabetic conditions. Hence, the Akt1-Notch3/YAP-ANGPT1/2 signaling cascade in VSMCs likely crucially regulates endothelial function via paracrine mechanisms.

Fig.2 Akt1-mediated regulation of ANGPT1 and ANGPT2 expression in vascular smooth muscle cells.^{2, 3}

• Anti-ANGPT1/ANGPT2 Antibody Modulation of Tumor

Prior investigations have documented diosmetin's anticancer properties against certain tumor types. Nevertheless, its potential anticancer effects, particularly its anti-angiogenic properties, in skin cancer remain ambiguous. To investigate the effects of diosmetin on angiogenesis, metastasis, and tumor growth in vivo, researchers have utilized a mouse melanoma model. Tumor tissues from diosmetin-treated and untreated mice are analyzed to assess changes in tumor vasculature. Immunostaining with anti-ANGPT2 reveals decreased ANGPT2 expression in diosmetin-treated mice, with the lowest levels detected in hypoxic intratumoral regions. These findings suggest that diosmetin induces normalization of tumor vasculature by reducing ANGPT2 levels and enhancing pericyte coverage, thereby inhibiting metastasis formation in the lungs and lymph nodes.

Creative Biolabs offers an extensive range of meticulously crafted anti-Angiopoietin antibodies, engineered using recombinant techniques. Moreover, personalized customization services are accessible to adapt neutralizing antibodies targeting Angiopoietins, like ANGPT1 and ANGPT2, to various requirements.

REFERENCES

1. Lukasz, Alexander, Philipp Kümpers, and Sascha David. "Role of angiopoietin/tie2 in critical illness: promising biomarker, disease mediator, and therapeutic target?" Scientifica 2012.1 (2012): 160174.
2. Ha, Jung Min, et al. "Akt1-dependent expression of angiopoietin 1 and 2 in vascular smooth muscle cells leads to vascular stabilization." Experimental & Molecular Medicine 54.8 (2022): 1133-1145.
3. Distributed under Open Access license CC BY 4.0, without modification.