Microbiële metaboliet 4EPS remt AT1R en verlaagt bloeddruk en aorta-aneurysmavorming

Hypertension, Volume 83, Issue 3, Page e25364, March 1, 2026. BACKGROUND:Plasma accumulation of the gut microbial metabolite 4-ethylphenylsulfate (4EPS), derived from dietary amino acid, tyrosine, has been associated with cardiovascular, renal, metabolic, and neurological disorders. AngII (angiotensin II) infusion increases circulating 4EPS in mice, suggesting a potential mechanistic role. We hypothesized that 4EPS modulates AngII-regulated pathophysiology and disease progression by directly inhibiting AT1R (angiotensin II type 1 receptor).METHODS:This hypothesis was tested by combining AT1R pharmacology, cell signaling assays, ex vivo vascular studies, an AngII-induced aortic aneurysm growth model, and plasma proteomics analysis.RESULTS:in vitro, 4EPS reduced the binding of both AngII and the antagonist candesartan to AT1R and suppressed AngII-induced calcium signaling. Ex vivo, 4EPS attenuated AngII-mediated vasoconstriction. In vivo, high-fat diet–fed ApoE-null mice coinfused with A