Combining three independent pathological stressors induces a heart failure with preserved ejection fraction phenotype
Yijia Li, Hajime Kubo, Daohai Yu, Yijun Yang, Jaslyn Johnson, Deborah Eaton, Remus M. Berretta, Michael Foster, Timothy A. McKinsey, Jun Yu, John W. Elrod, Xiongwen Chen, Steven R. Houser
Abstract
Our study shows that three independent pathological stressors (increased Ca 2+ influx, high-fat diet, and l-NAME) together produce a profound HFpEF phenotype. The primary mechanisms include HDAC-dependent-CM hypertrophy, necrosis, increased M 2 -macrophage population, fibroblast activation, and myocardial fibrosis. A role for HDAC activation in the HFpEF phenotype was shown in studies with SAHA treatment, which prevented the severe HFpEF phenotype. This “3-Hit” mouse model could be helpful in identifying novel therapeutic strategies to treat HFpEF.
Topics & Concepts
PhenotypeHeart failure with preserved ejection fractionPathologicalHeart failureMedicineFibrosisStressorPopulationInternal medicineMuscle hypertrophyEjection fractionCardiologyEndocrinologyBiologyGeneticsGeneClinical psychologyEnvironmental healthHeart Failure Treatment and ManagementCardiovascular Function and Risk FactorsCardiac Structural Anomalies and Repair