Gut microbiota dysfunction mediates stress-exacerbated aortic dissection via the bacteroides vulgatus-outer membrane vesicles-stearic acid-JNK/MAPK axis - PubMed
3 hours ago
- #gut microbiota
- #aortic dissection
- #chronic stress
- Chronic restraint stress (CRS) exacerbates aortic dissection in mice, accelerating aortic dilation, increasing mortality, and promoting a synthetic phenotype in vascular smooth muscle cells (VSMCs).
- CRS reduces gut microbiota diversity, specifically depleting Bacteroides vulgatus. Lower abundance of B. vulgatus correlates with more severe aortic dissection.
- Depleting the gut microbiota with antibiotics mitigates stress-aggravated aortic dissection, while fecal microbiota transplantation from stressed mice worsens it.
- Metabolomic analysis identifies stearic acid as a key metabolite, derived from outer membrane vesicles of B. vulgatus, negatively correlated with aortic diameter.
- Stearic acid supplementation inhibits synthetic VSMC transformation, reduces aortic dissection incidence, and suppresses JNK/MAPK pathway activation.
- Mechanistically, stearic acid attenuates AngII-induced JNK phosphorylation in VSMCs in vitro, an effect reversed by a JNK agonist.
- Targeting the gut microbiota-B. vulgatus-stearic acid axis may offer a novel therapeutic strategy for stress-aggravated aortic dissection.