biostudies-literatureMallaredy VNHLBI NIH HHS280-297https://www.ebi.ac.uk/biostudies/studies/S-EPMC11223950biostudies-literatureUnknown135(2)<h4>Background</h4>Heart failure (HF) is one of the leading causes of mortality worldwide. Extracellular vesicles, including small extracellular vesicles or exosomes, and their molecular cargo are known to modulate cell-to-cell communication during multiple cardiac diseases. However, the role of systemic extracellular vesicle biogenesis inhibition in HF models is not well documented and remains unclear.<h4>Methods</h4>We investigated the role of circulating exosomes during cardiac dysfunction and remodeling in a mouse transverse aortic constriction (TAC) model of HF. Importantly, we investigate the efficacy of tipifarnib, a recently identified exosome biogenesis inhibitor that targets the critical proteins (Rab27a [Ras associated binding protein 27a], nSMase2 [neutral sphingomyelinase 2], Circulation researchTipifarnib Reduces Extracellular Vesicles and Protects From Heart Failure.PMC11223950P01 HL147841R01 HL169405R01 HL143892P01 HL134608R01 HL091983Joladarashi DMagadum AKoch WJIbetti JGarikipati VNSCheng ZCimini MBenedict CTruongcao MMallaredy VRoy RThej CGonzalez CKishore RfalseTipifarnib Reduces Extracellular Vesicles and Protects From Heart Failure.<h4>Background</h4>Heart failure (HF) is one of the leading causes of mortality worldwide. Extracellular vesicles, including small extracellular vesicles or exosomes, and their molecular cargo are known to modulate cell-to-cell communication during multiple cardiac diseases. However, the role of systemic extracellular vesicle biogenesis inhibition in HF models is not well documented and remains unclear.<h4>Methods</h4>We investigated the role of circulating exosomes during cardiac dysfunction and remodeling in a mouse transverse aortic constriction (TAC) model of HF. Importantly, we investigate the efficacy of tipifarnib, a recently identified exosome biogenesis inhibitor that targets the critical proteins (Rab27a [Ras associated binding protein 27a], nSMase2 [neutral sphingomyelinase 2], 2024-01-01T00:00:00Z2024 Jul2026-06-02T08:44:32.322Z2026-04-16T03:12:46.98ZS-EPMC112239503884708010.1161/circresaha.123.32411010.1161/CIRCRESAHA.123.324110