Authors: Tsunehisa Yamamoto, Kirill Batmanov, Elizabeth Pruzinsky, Yang Xiao, Swapnil V Shewale, Kendra McDaid, Teresa C Leone, Santosh K Maurya, E Douglas D Lewandowski, Daniel P Kelly
Published: 2021-11-22
DOI: 10.1161/res.129.suppl_1.113
Source: Full article
During the development of heart failure (HF), the PPAR/ERR complex becomes deactivated resulting in diminished capacity for mitochondrial fatty acid oxidation (FAO) and ATP production leading to an “energy-starved” state that contributes to progression of HF. Receptor-Interacting protein 140 (RIP140) serves as a co-repressor of PPAR/ERR in some extra-cardiac tissues. We hypothesized that inhibition of RIP140 would re-activate PPAR/ERR enhancing capacity for fuel catabolism and ATP production in the failing heart. Heart and skeletal muscle-specific RIP140 knockout mice (strRIP140KO) were resistant to the development of cardiac hypertrophy and diastolic dysfunction in response to chronic pressure overload that mimicked features of HF with preserved ejection fraction (HFpEF). To further evaluate the role of RIP140 in heart, cardiac-specific (cs) RIP140KO mice were generated.