PTEN and heart failure: For instance, miR-21 sustains fibroblast activation via PTEN/Akt signaling, with preclinical antagomirs showing 40% fibrosis reduction[116]; miR-34a promotes cardiomyocyte senescence by suppressing SIRT1, correlating with diastolic stiffness in human heart failure with preserved ejection fraction[117]; miR-199a-5p elevation post-MI predicts adverse remodeling through Bcl-2-mediated apoptosis resistance.[118] These miRNA networks interface with discussed hubs-TGF-β/Smad pathway upregulated by miR-21, while NF-κB transcriptionally activates miR-34a clusters.[119]