# Systemic angiogenic protein changes following propranolol therapy in infantile hemangioma: a multi-target perspective

## TL;DR

Propranolol treatment for infantile hemangioma rebalances angiogenic proteins, offering new insights into its therapeutic effects and potential biomarkers.

## Contribution

The study reveals novel systemic angiogenic protein changes and their biological pathways modulated by propranolol in infantile hemangioma.

## Key findings

- Twenty-six angiogenic proteins were significantly downregulated in untreated IH patients.
- Six proteins were significantly upregulated after three months of propranolol treatment.
- Bioinformatic analysis linked these proteins to key pathways like VEGF signaling and ERBB-EGFR axis.

## Abstract

Infantile hemangioma (IH) is a common benign vascular tumor in infants, often requiring intervention due to potential functional impairment and cosmetic concerns. Propranolol, a nonselective β-adrenergic receptor blocker, is the first-line therapy for IH, yet its mechanisms remain incompletely elucidated.

This prospective study investigated the systemic angiogenic protein profile changes in response to propranolol in 14 treatment-naïve IH infants compared to 14 healthy controls using antibody array analysis.

We identified twenty-six angiogenic proteins significantly downregulated in pretreatment IH patients compared to healthy controls. After 3 months of propranolol treatment, six proteins including HB-EGF, TGFα, ANGPTL4, Follistatin, Tie-1 and PLGF were significantly upregulated. Bioinformatic enrichment analysis revealed that these proteins are involved in key biological processes and signaling pathways, including epithelial cell proliferation, angiogenesis regulation, VEGF signaling, ERBB-EGFR axis, Ras-MAPK, and PI3K-Akt pathways.

These results suggest that propranolol treatment is associated with a rebalancing of dysregulated angiogenic proteins in IH, through modulating both pro- and anti-angiogenic factors to rebalance vascular homeostasis. Our study provides novel insights into the systems-level pharmacological actions of propranolol and proposes potential biomarkers for treatment response evaluation.