Stiffening

Cardiology

Biology

Endocrinology

Metabolite

Internal medicine

Composite material

Trimethylamine N-oxide

Isolated systolic hypertension

Medicine

Biochemistry

Trimethylamine

Bioinformatics

Blood pressure

Materials science

Microbiome

Pulse pressure

Physiology

Hypertension

Aging is associated with stiffening of the large elastic arteries and consequent increases in systolic blood pressure (SBP), which together increase cardiovascular disease risk; however, the upstream mechanisms are incompletely understood. Using complementary translational approaches in mice and humans, we investigated the role of the gut microbiome-derived metabolite trimethylamine N-oxide (TMAO) in age-related aortic stiffening and increased SBP. Aortic stiffness was measured using carotid-femoral or aortic pulse wave velocity (PWV) in humans and mice, respectively. Study 1: Plasma TMAO concentrations were elevated ( P &lt;0.001) in healthy middle-aged to older (6.3±5.8 µmol/L) versus young (1.8±1.4 µmol/L) humans and positively related to carotid-femoral PWV ( r 2 =0.15, P &lt;0.0001) and SBP ( r 2 =0.09, P &lt;0.001), independent of traditional cardiovascular risk factors. Study 2: Dietary supplementation with TMAO increased aPWV in young mice and exacerbated the already elevated aPWV of old mice, accompa...

Gut Microbiome-Derived Metabolite Trimethylamine N-Oxide Induces Aortic Stiffening and Increases Systolic Blood Pressure With Aging in Mice and Humans