Renal denervation attenuates cardiac dysfunction in HFpEF by inhibiting the ATP-P2X7-NLRP3 inflammasome axis.

ABSTRACT: Heart failure with preserved ejection fraction (HFpEF) arises from intersecting comorbidities involving inflammation, metabolic stress, and sympathetic nervous system (SNS) activation. To mirror this complexity, we established a clinically oriented 3-hit mouse model combining advanced age, a high-fat diet, and chronic NOS inhibition with NG-Nitro-L-arginine methyl ester (L-NAME). We tested whether renal denervation (RDN) mitigates HFpEF by blunting SNS outflow and the ATP-P2X7-NLRP3 inflammasome axis, and in parallel probed the contribution of this pathway using pharmacologic and cellular approaches. 3-hit mice developed preserved ejection fraction with diastolic dysfunction, cardiomyocyte hypertrophy, interstitial fibrosis, impaired exercise capacity, and elevated inflammatory cytokines,

SUBMITTER: Li Z 

PROVIDER: S-EPMC12680762 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature