# CYP1A1/20-HETE/GPR75 Axis-Mediated Arachidonic Acid Metabolism Dysregulation in H-Type Hypertension Pathogenesis

## TL;DR

This study identifies a key metabolic pathway involving arachidonic acid that may contribute to H-type hypertension, offering potential new treatment targets.

## Contribution

The study reveals a novel role of the CYP1A1/20-HETE/GPR75 axis in dysregulating arachidonic acid metabolism in H-type hypertension.

## Key findings

- High-methionine diets reduce arachidonic acid levels, which are restored by folic acid.
- Methionine upregulates CYP1A1 and GPR75 genes, linked to hypertension pathology.
- Population data supports a correlation between essential fatty acids and H-type hypertension.

## Abstract

This study aims to explore the pathogenic mechanism of H-type hypertension. A rat model of H-type hypertension was established through high-methionine dietary intervention, with subsequent folic acid administration. Untargeted serum metabolomic profiling identified a significant reduction in arachidonic acid (AA) levels in the methionine-enriched group, which were effectively normalized following folic acid supplementation. Transcriptomic analysis revealed methionine-induced upregulation of AA pathway-associated genes Cyp1a1 and Gpr75. In contrast, after the intervention with folic acid, a downregulation of these genes was observed. These findings were corroborated through Western blotting and RT-qPCR validation. In vitro studies using EA.hy926 endothelial cells demonstrated that methionine exposure significantly elevated CYP1A1 expression. Furthermore, methionine stimulation induced marked upregulation of GPR75 and its downstream signaling components (NRAS, MEK1, and ERK1). Population-level evidence from the U.S. NHANES database substantiated significant correlations between essential fatty acids (AA, LA, and GLA) and H-type hypertension prevalence. Our research findings suggest that the CYP1A1/20-HETE/GPR75 axis-mediated dysregulation of AA metabolism may be one of the key pathological mechanisms of H-type hypertension. The research results provide clues for the discovery of new therapeutic targets for H-type hypertension.