Targeting endothelial vascular cell adhesion molecule-1 in atherosclerosis: drug discovery and development of vascular cell adhesion molecule-1–directed novel therapeutics

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 VCAM-1 function blocks monocyte infiltration into the subendothelial 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 downregulate 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.

Efficacy, tolerability, and safety of teverelix DP in patients with advanced prostate cancer: A multicenter, open‐label, phase 2 trial

“…In addition, a recent study in a mouse model of atherosclerosis (ApoE −/− mice) found that FSH accelerated atherosclerosis progression by promoting pro‐inflammatory cytokines and the migration of macrophages 46 . In another study, FSH also exacerbated atherosclerosis in ApoE −/− mice, and in a cell model of endothelial injury model (human umbilical vein endothelial cells) FSH promoted the expression of vascular cell adhesion molecule 1, 47 a transmembrane molecule involved in inflammation, vascular dysfunction and increased CV risk 48,49 …”

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