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Pan‐Histone deacetylase inhibition (HDACi) prevents heart failure with preserved ejection fraction (HFpEF) and cardiac fibrosis in high‐salt (HS) fed Dahl S rats (DS)
Author(s) -
Plato Craig F,
Perry Amy M,
Joly Kristin M,
Glascock Christopher,
Cavasin Maria A
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.782.1
Subject(s) - medicine , heart failure , cardiac fibrosis , fibrosis , cardiology , diastole , ejection fraction , heart failure with preserved ejection fraction , muscle hypertrophy , endocrinology , myocardial fibrosis , blood pressure
Chronic arterial hypertension (HYP) elicits cardiac hypertrophy and ultimately HFpEF, and >50% of patients diagnosed with heart failure have HFpEF. DS rats develop HYP, cardiac fibrosis and impaired cardiac diastolic performance in response to chronic HS feeding. HDACi is reported to decrease pathological cardiac hypertrophy, gene expression, and cardiac fibrosis. We evaluated the dose‐dependent effects of Scriptaid, a pan‐HDACi, to inhibit HFpEF and cardiac fibrosis in response to sustained HYP. DS were fed normal (0.49% NaCl) or HS (4.0% NaCl) and administered Scriptaid (3, 10, 30 mg/kg, i.p.) or vehicle (100% DMSO) daily for 6 wks. HS time‐dependently induced cardiac hypertrophy (endpoint: 26%) and impaired indices of diastolic performance (mitral Doppler E/A: −27% and isovolumic relaxation time: +30%) while not affecting left ventricular (LV) ejection fraction, and was associated with increased LV ANF and α‐skeletal actin mRNA expression and interstitial fibrosis (83%). Scriptaid dose‐dependently prevented reductions in diastolic performance and attenuated LV hypertrophy, interstitial fibrosis, and pathological gene expression despite not influencing severity of HYP. These results suggest HDACi may epigenetically modulate cardiac structural and functional remodeling responses to arterial hypertension thus improving cardiac performance in salt‐sensitive hypertension‐induced HFpEF.