Angiostatin: a promising therapeutic target for atopic dermatitis

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.