Angiostatin: a promising therapeutic target for atopic dermatitis

Abstract

Angiostatin, a 38–45 KDa proteolytic fragment derived from plasminogen, has garnered significant attention for its dual roles in inhibiting angiogenesis and modulating inflammation. We employed bidirectional Mendelian randomization (MR), meta-analysis, and colocalization to investigate the causal relationship between angiostatin and atopic dermatitis (AD) using three angiostatin and two AD datasets. Additionally, we analyzed global epidemiological trends (1990–2021) and performed transcriptomic profiling of AD. MR analyses revealed a protective effect of angiostatin on AD risk (combined odds ratio: 0.9437, 95% confidence interval [CI]: 0.9198–0.9683, p < 0.0001), while reverse analyses showed no association (standardized mean difference: -0.0029, 95% CI: -0.0516-0.0459, p = 0.9084). Colocalization indicated no shared causal variants (H4 probabilities < 80%). Epidemiological trends highlighted declining age-standardized AD rates despite rising case numbers. Transcriptomic analyses implicated NF-κB, PI3K-Akt, and JAK-STAT pathways in AD pathogenesis. These findings position angiostatin as a dual-action therapeutic candidate, offering novel opportunities to simultaneously target vascular remodeling and immune dysregulation in AD. Translational research is warranted to harness its clinical potential.