Targeting endothelial vascular cell adhesion molecule-1 in atherosclerosis: drug discovery and development of vascular cell adhesion molecule-1–directed novel therapeutics
2023/08/18 by Jessica R Pickett, Yuao Wu, Lucia F Zacchi +3 · 27 citations
Medicine · Immunology and Microbiology · #Cell Adhesion Molecules Research #Atherosclerosis and Cardiovascular Diseases #Phagocytosis and Immune Regulation
paper · pdf · doi:10.1093/cvr/cvad130
Abstract
Vascular cell adhesion molecule-1 (VCAM-1) has been well established as a critical contributor to atherosclerosis and consequently as an attractive therapeutic target for anti-atherosclerotic drug candidates. Many publications have demonstrated that disrupting the VCAM-1 function blocks monocyte infiltration into the sub-endothelial space, which effectively prevents macrophage maturation and foam cell transformation necessary for atherosclerotic lesion formation. Currently, most VCAM-1-inhibiting drug candidates in pre-clinical and clinical testing do not directly target VCAM-1 itself but rather down-regulate its expression by inhibiting upstream cytokines and transcriptional regulators. However, the pleiotropic nature of these regulators within innate immunity means that optimizing dosage to a level that suppresses pathological activity while preserving normal physiological function is extremely challenging and oftentimes infeasible. In recent years, highly specific pharmacological strategies that selectively inhibit VCAM-1 function have emerged, particularly peptide- and antibody-based novel therapeutics. Studies in such VCAM-1-directed therapies so far remain scarce and are limited by the constraints of current experimental atherosclerosis models in accurately representing the complex pathophysiology of the disease. This has prompted the need for a comprehensive review that recounts the evolution of VCAM-1-directed pharmaceuticals and addresses the current challenges in novel anti-atherosclerotic drug development.
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