Vascular Adhesion Proteins in Inflammatory Processes

Vascular adhesion proteins constitute a specialised class of endothelial surface molecules that orchestrate the recruitment of leukocytes to sites of tissue injury or infection. Among these, vascular adhesion protein-1 (VAP-1) is unique in combining adhesion functions with semicarbazide-sensitive amine oxidase activity, generating hydrogen peroxide and aldehydes that amplify local inflammatory signals. In concert with immunoglobulin-superfamily members such as intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), VAP-1 mediates sequential tethering, firm adhesion and transmigration of circulating leukocytes. Dysregulated expression or activity of these adhesion proteins underlies chronic inflammatory diseases—from atherosclerosis and autoimmune arthritis to hepatic cirrhosis and chronic obstructive pulmonary disease. Ongoing efforts aim to exploit VAP-1 as both an imaging target and therapeutic node, with small-molecule inhibitors and targeted tracers offering potential for improved diagnosis and treatment.

Research from Nature Portfolio

In preclinical models of chronic arthritis, a novel VAP-1/SSAO inhibitor demonstrated potent anti-inflammatory and analgesic effects without inducing cartilage damage, attenuating joint swelling and reducing pro-inflammatory chemokine release. In human carotid atherosclerotic plaques and murine lesions, functional VAP-1 was localised to endothelial cells of neovessels, enabling non-invasive detection by a sialic-acid binding immunoglobulin-like lectin-9 PET tracer and correlating uptake with macrophage density. In cholesterol-fed rabbits, selective blockade of VAP-1’s amine oxidase activity lowered hydrogen peroxide generation in the arterial wall, diminished macrophage recruitment and smooth muscle proliferation, and significantly reduced plaque burden. Collectively these studies elucidate mechanistic roles for VAP-1 in leukocyte trafficking and oxidative stress while validating both imaging and inhibitor strategies for translation.

Vascular Adhesion Proteins in Inflammatory Processes publication trend

The graph below shows the total number of articles in vascular adhesion proteins in inflammatory processes across all publications each year (not limited to Nature Index journals).

Technical terms

Vascular adhesion protein-1 (VAP-1): A dual-function endothelial glycoprotein with adhesion properties and semicarbazide-sensitive amine oxidase activity, critical for leukocyte recruitment.

Intercellular adhesion molecule-1 (ICAM-1): An immunoglobulin-superfamily ligand on endothelial cells that binds leukocyte integrins to support firm adhesion under flow.

Vascular cell adhesion molecule-1 (VCAM-1): An endothelial ligand for integrin α4β1, facilitating leukocyte retention and extravasation in inflamed tissues.

Leukocyte extravasation: The stepwise process by which white blood cells exit the bloodstream—rolling, adhesion and transmigration—into affected tissue.

Semicarbazide-sensitive amine oxidase (SSAO): The catalytic activity of VAP-1 that oxidatively deaminates primary amines, generating reactive species that modulate vascular inflammation.

References

1. Serum Vascular Adhesion Protein-1 and Endothelial Dysfunction in Hepatic Cirrhosis: Searching for New Prognostic Markers. International Journal of Molecular Sciences (2024).
2. Vascular Adhesion Protein-1 (VAP-1)/Semicarbazide-Sensitive Amine Oxidase (SSAO): A Potential Therapeutic Target for Atherosclerotic Cardiovascular Diseases. Frontiers in Pharmacology (2021).
3. Analgesic and Anti-Inflammatory Effects of the Novel Semicarbazide-Sensitive Amine-Oxidase Inhibitor SzV-1287 in Chronic Arthritis Models of the Mouse. Scientific Reports (2017).
4. Leukocyte trafficking-associated vascular adhesion protein 1 is expressed and functionally active in atherosclerotic plaques. Scientific Reports (2016).
5. First-in-Human Study of 68Ga-DOTA-Siglec-9, PET Ligand Targeting Vascular Adhesion Protein 1. Journal of Nuclear Medicine (2020).
6. Inhibition of Semicarbazide-sensitive Amine Oxidase Reduces Atherosclerosis in Cholesterol-fed New Zealand White Rabbits. Scientific Reports (2018).