Premium
Adverse Cardiac Effects Due to Cardiac Specific Disruption of the Nuclear Receptor Corepressor 1 (NCOR1)
Author(s) -
Zhang Jie,
Vatner Dorothy E.,
Vatner Stephen F.
Publication year - 2018
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.2018.32.1_supplement.848.2
Subject(s) - pressure overload , corepressor , heart failure , cardiology , medicine , cardiac function curve , ejection fraction , diastole , nuclear receptor , biology , blood pressure , cardiac hypertrophy , transcription factor , biochemistry , gene
Disruption of the nuclear receptor corepressor 1 (NCOR1) knockout (KO), a transcriptional coregulatory, has been shown to exert only beneficial effects on disease processes, particularly in skeletal muscle, e.g., it improves exercise endurance, insulin sensitivity and reduces inflammation. The goal of this investigation was to determine if the cardiac specific NCOR1 KO also protects the heart against the stress of chronic pressure overload, induced by chronic thoracic aortic constriction. Baseline cardiac function, as reflected by left ventricular (LV) ejection fraction (EF), assessed echocardiographically, was similar in NCOR1 KO mice (62±2%) and their wild type (WT) littermates (68±1%). Surprisingly, after one week of pressure overload, induced by thoracic aortic banding, cardiac function deteriorated significantly more in NCOR1 KO than in their WT controls. LV EF was significantly less (31±7.4%), p<0.01, in NCOR1 KO than WT (59±3.1%) with higher LV end diastolic diameter (4.0±0.3 mm), compared to WT (3.4±0.2 mm). Survival rate was lower (60%) in NCOR1 KO with 1 week of pressure overload than WT, which all survived. At autopsy, lung/body weight, an index of heart failure, was also greater, p<0.01, in NCOR1 KO mice (10±0.7) vs. WT (6.5±0.4); confirmed by similar results for lung/tibial length. Histological analysis demonstrated greater fibrosis, reflecting greater cell death in NCOR1 KO compared with WT controls. Thus, the salutary features of other NCOR1 KOs could not be recapitulated in the heart with the stress of chronic pressure overload, where the cardiac specific NCOR1 KO actually fared worse with exacerbation of heart failure and mortality. Support or Funding Information N/A This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .