The role of arachidonic acid metabolites in the subtype classification and pathogenesis of primary aldosteronism

Mei You; Li Li; Xintao Tan; Xiaoli Liu; Lijuan Wang; Tingbing Cao; Bowen Wang; Min Liu; Yue Gao; Qing Zhou; Ruomei Yang; Weihua Lan; Peng Gao; Zhiming Zhu; Zhencheng Yan

doi:10.1016/j.isci.2025.114598

The role of arachidonic acid metabolites in the subtype classification and pathogenesis of primary aldosteronism

iScience. 2025 Dec 31;29(2):114598. doi: 10.1016/j.isci.2025.114598. eCollection 2026 Feb 20.

Authors

Mei You¹, Li Li¹, Xintao Tan², Xiaoli Liu¹, Lijuan Wang¹, Tingbing Cao¹, Bowen Wang¹, Min Liu¹, Yue Gao¹, Qing Zhou¹, Ruomei Yang¹, Weihua Lan², Peng Gao¹, Zhiming Zhu^{1

3}, Zhencheng Yan¹

Affiliations

¹ Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Chongqing Key Laboratory of Metabolic Vascular Diseases, Daping Hospital, Army Medical University, Chongqing Institute of Hypertension, Chongqing 400042, China.
² Department of Urology, Daping Hospital, Army Medical University, Chongqing 400042, China.
³ Chongqing Institute of Brain and Science, Chongqing 400042, China.

Abstract

Primary aldosteronism (PA) is a common form of secondary hypertension with a complex diagnostic process and incompletely understood pathogenesis. In this controlled cross-sectional study, metabolomic profiling of 37 patients with bilateral PA, 38 with unilateral PA, and 20 with essential hypertension (EH) revealed that the most prominent metabolic difference lies in lipid metabolism, particularly arachidonic acid (AA) metabolism. We identified a panel of AA metabolites that improved PA subtyping. Additionally, levels of most AA metabolites were markedly reduced in PA patients after curative adrenal ablation. Mechanistically, treatment with AA enhanced the uptake of calcium ions and stimulated the proliferation and migration of adrenal cortical cells, with increased expressions of aldosterone synthase CYP11B2 and the calcium ion channel transient receptor potential canonical 3 (TRPC3). Furthermore, an inhibitor of TRPC3, pyr3, blocked these effects of AA. These findings elucidate the role of AA metabolites in PA pathogenesis and highlight them as potential targets for therapeutic intervention.

Keywords: endocrinology; molecular biology; omics; pharmacology.