Hypertension-Associated Acetate Deficiency Enhances Platelet Activation and Thrombosis Via Olfr78

BACKGROUND: Arterial thrombotic events constitute the leading cause of mortality in hypertension. Gut dysbiosis induces endothelial dysfunction and systemic inflammation, contributing to hypertension and its associated cardiovascular complications. Whether these dysbiotic microbiota metabolites in hypertension directly regulate platelet hyperactivation and thrombosis remains unclear. METHODS: -induced mesenteric arteriole thrombosis model, ex vivo microfluidic whole-blood perfusion assay, and in vitro platelet functional studies defined the functional effects of acetate on platelet activation. Moreover, platelet-specific Olfr78 (olfactory receptor 78)-deficient mice were employed to explore the underlying mechanisms of acetate on platelet activation. RESULTS: mobilization as well as inactivating RhoA/ROCK2/MLC (myosin light chain) signaling to inhibit platelet activation. A high-fiber diet upregulated acetate/Olfr78 signaling in platelets to suppress microvascular thrombosis and protect against myocardial injury during myocardial infarction in mice. CONCLUSIONS: Acetate is a negative regulator of platelet hyperreactivity and thrombus formation via the Olfr78 receptor, and acetate deficiency contributes to platelet hyperreactivity in hypertension. Lifestyle modifications, particularly high-fiber dietary intervention and acetate supplementation, exhibit potent antithrombotic effects in hypertension.