# Exploiting porphyrin metabolism to inhibit angiogenesis

## TL;DR

This paper shows that disrupting heme and porphyrin metabolism in endothelial cells can inhibit blood vessel growth, offering a potential treatment for diseases with abnormal blood vessel formation.

## Contribution

The study reveals a novel pharmacological approach using ALA to inhibit angiogenesis by targeting porphyrin metabolism in endothelial cells.

## Key findings

- ALA treatment caused porphyrin accumulation and reduced endothelial cell proliferation and migration.
- Extracellular porphyrins contributed to anti-angiogenic effects in both ex vivo and in vivo models.
- ALA inhibited pathological neovascularization in a mouse model of retinopathy.

## Abstract

Heme is an essential iron-containing porphyrin that plays a critical role in endothelial cell (EC) function, regulating processes such as cell signalling and energetic metabolism. Nevertheless, the role of de novo heme synthesis and porphyrin metabolism during angiogenesis remains poorly understood. In this study, a pharmacological approach using 5-aminolevulinic acid (ALA) was employed to dysregulate heme/porphyrins homeostasis in EC. ALA treatment resulted in intracellular porphyrins accumulation and extensive release into the extracellular environment. ALA-treated EC exhibited diminished proliferation and migration, as well as reduced ability to form tubule-like structures, which led to impaired ex vivo angiogenic sprouting and in vivo angiogenesis in the developing retina. Moreover, ALA inhibited pathological neovascularization in the oxygen-induced retinopathy mouse model that recapitulates the vascular alterations occurring in human patients affected by retinopathy of prematurity and diabetic retinopathy. Importantly, extracellular porphyrins contributed to the observed anti-angiogenic effects. These findings underscore the biological impact of endogenous porphyrins on EC function and angiogenesis, providing insights into potential therapeutic applications for human diseases characterized by aberrant vascularization, including neovascular eye diseases.

The online version of this article (10.1007/s10456-026-10034-y) contains supplementary material, which is available to authorized users.