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

Background: 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. Methods: Angiogenesis was assessed in Angiotensin II (AngII)-induced hypertensive mice and endothelial cells using Results: 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. Conclusion: 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.