The blood pressure-lowering effect of an anti-soluble epoxide hydrolase vaccine in angiotensin II-induced hypertension in mice.

We developed a soluble epoxide hydrolase (sEH) vaccine as a novel therapeutic strategy against hypertension. A placebo-controlled study was conducted to investigate its efficacy. Fifty-five wild-type mice were randomly divided into three groups: control (n = 5), angiotensin Ⅱ (Ang II) induced hypertension with vaccine (n = 23) and without vaccine (n = 24). Hypertension was induced by subcutaneous Ang II infusion via an osmotic mini pump, whereas controls received saline. Vaccinations were administered at 8, 10, 12, and 14 weeks of age. Ang II significantly increased systolic and diastolic blood pressure both in hypertension groups; however, vaccination significantly mitigated this rise. Mean reductions were - 8 ± 2 mmHg (systolic) and - 5 ± 2 mmHg (diastolic). Vaccinated mice also exhibited reduce myocardial hypertrophy and smaller aortic diameters. These findings indicate that anti-sEH vaccination suppresses hypertension and associated cardiovascular remodeling, indicating its potential as a long-acting therapeutic option. The proposed mechanism of anti-sEH vaccination. Anti-sEH vaccination induces sEH antibody production, thereby inhibiting sEH activity, leading to increased EETs and reduced DHETs. The vaccination attenuates Angiotensin II-induced cardiac hypertrophy and aortic dilatation. CYP450 cytochrome P450, EETs epoxyeicosatrienoic acids, sEH soluble epoxide hydrolase, DHETs dihydroxyeicosatrienoic acids.