PT357 Angiotensin-receptor neprilysin-inhibition (ARNi) attenuates ischemic cardiac failure in vivo and angiotensin-II-induced cellular cardiac hypertrophy and fibrosis

Abstract

and TGF-b1; and TGF-b1, respectively, for 48 hours before harvesting. Cardiac myocyte hypertrophy, fibroblast and RMC collagen synthesis were determined by [H]-leucine and [H]-proline incorporation, respectively. Results: VCP746 reduced IL-1band TNF-a-stimulated NCM hypertrophy (85.1 4.3% and 91.7 3.1% of unstimulated control, respectively; VCP746 10 M; P < 0.0001 vs. IL1b and TNF-a alone) in a concentration-dependent manner. VCP746 also concentrationdependently reduced AngIIand TGF-b1-mediated NCF collagen synthesis (104.8 5.1% and 142.8 4.8% of unstimulated control, respectively; VCP746 10 M; P < 0.05 vs. AngII alone, P < 0.0001 vs. TGF-b1 alone). TGF-b1-stimulated RMC collagen synthesis was also inhibited in a concentration-dependent manner by VCP746 (105.9 4.5% of unstimulated control; VCP746 10 M; P < 0.0001 vs. TGF-b1 alone). MTT assay showed that VCP746 had no effects on cell viability. Conclusion: This study has demonstrated that the A1/A2 adenosine receptor agonist, VCP746, can reduce cardiac hypertrophy and fibrosis, as well as renal fibrosis. Targeting adenosine receptors may represent a novel therapeutic approach to the management of heart failure and associated renal fibrosis. Disclosure of Interest: None Declared