Zinc-mediated Inhibition of Soluble Epoxide Hydrolase Promotes Pulmonary Hypertension.

ABSTRACT: Rationale: Pulmonary hypertension (PH) and vascular remodeling involve complex molecular mechanisms, with zinc and epoxyeicosatrienoic acids playing key roles. Objectives: We sought to investigate whether zinc-mediated inhibition of soluble epoxide hydrolase contributes to the development of PH and vascular remodeling under hypoxic conditions. Methods: Activity assays measured zinc-mediated soluble epoxide hydrolase inhibition, with mutagenesis and inductively coupled mass spectrometry identifying key cysteines. Pulmonary arteries and human pulmonary artery smooth muscle cells were used to measure vasoconstriction in response to epoxyeicosatrienoic acid, zinc, soluble epoxide hydrolase inhibition, or hypoxia treatment. A C230A knockin mouse was generated to elucidate t

SUBMITTER: Simoes de Jesus D 

PROVIDER: S-EPMC12499926 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature