# BACH1-mediated transcriptional repression of pro-angiogenic factors drives angiogenic impairment in hypertension

## TL;DR

This study shows that BACH1 suppresses pro-angiogenic genes in hypertension, impairing blood vessel growth and contributing to high blood pressure.

## Contribution

The study identifies BACH1 as a novel transcriptional repressor linking hypertension to impaired angiogenesis.

## Key findings

- BACH1 upregulation in hypertensive mice and endothelial cells suppresses pro-angiogenic genes like FGF1, VEGFA, ANGPT1, and AGGF1.
- Reduced circulating levels of these pro-angiogenic factors correlate with higher blood pressure in patients.
- Endothelial BACH1 knockdown restores angiogenesis and reduces hypertension in mice.

## Abstract

Impaired angiogenesis is a well-recognized pathophysiological feature of hypertension, yet the molecular mechanisms linking elevated blood pressure to angiogenic impairment remain incompletely understood. Endothelial transcriptional regulation may play a critical role in this process.

Angiogenesis was assessed in Angiotensin II (AngII)-induced hypertensive mice and endothelial cells using in vivo and in vitro approaches. BACH1 expression and regulation were examined following AngII stimulation. Transcriptional repression by BACH1 was investigated at pro-angiogenic gene promoters. Circulating angiogenic factors were measured in hypertensive patients and analyzed in relation to blood pressure. Endothelial-enriched BACH1 knockdown was performed in vivo to evaluate its effects on angiogenesis and blood pressure.

Angiogenesis was significantly impaired in AngII-induced hypertensive mice and endothelial cells, accompanied by marked upregulation of BACH1. Mechanistically, BACH1 acted as a direct transcriptional repressor by binding to the promoters of key pro-angiogenic factors, including FGF1, VEGFA, ANGPT1 and AGGF1, thereby suppressing their expression. Consistently, circulating levels of these factors were reduced in hypertensive patients and negatively correlated with blood pressure. Importantly, endothelial-enriched BACH1 knockdown restored retinal angiogenesis and significantly attenuated hypertension development in AngII-treated mice.

These findings identify BACH1 as a critical transcriptional regulator linking hypertension to impaired angiogenesis and suggest that targeting endothelial BACH1 may represent a potential therapeutic strategy for hypertension.