title: Inhibitory kappa-B kinase-β inhibition prevents adaptive left ventricular hypertrophy.
abstract: BACKGROUND
  Most cardiovascular studies have implicated the central transcription factor nuclear factor kappa-B (NF-κB) as contributing to the detrimental effects of cardiac injury. This ostensibly negative view of NF-κB competes with its important role in the normal host inflammatory and immune response. Pressure overload, left ventricular hypertrophy (LVH), and heart failure represent a spectrum of disease that has both adaptive and maladaptive components. In contrast to its known effects related to myocardial ischemia-reperfusion, we hypothesized that NF-κB is necessary for the compensatory phase of cardiac remodeling.
  
  
  METHODS
  C57BL6 mice underwent minimally invasive transverse aortic constriction with or without inhibition of the proximal NF-κB kinase, inhibitory kappa-B kinase-β. Isolated cardiomyocytes were cultured. Transthoracic echocardiography was performed on all mice.
  
  
  RESULTS
  Inhibitory kappa-B kinase-β inhibition successfully decreased cardiomyocyte expression of phosphorylated p65 NF-κB and decreased expression of hypertrophic markers with stimulation in vitro. Three weeks after transverse aortic constriction, the mice treated with inhibitory kappa-B kinase-β inhibition more aggressively developed LVH, as measured by heart weight/body weight ratio, left ventricular mass, and wall thickness. These mice also demonstrated a functional decline, as measured by decreased fractional shortening and ejection fraction. These findings were associated with decreased protein expression of p65 NF-κB.
  
  
  CONCLUSIONS
  Although short-term pressure-overload results in compensatory LVH with normal cardiac function, NF-κB inhibition resulted in increased LVH that was associated with functional deterioration. These observations suggest that NF-κB is an important part of the adaptive phase of LVH, and its inhibition detrimentally affects cardiac remodeling.
authors.affiliation: Department of Surgery, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Nancy M
authors.initials: NM
authors.lastname: Andersen
authors.forename: Ruhang
authors.initials: R
authors.lastname: Tang
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.forename: Hadi
authors.initials: H
authors.lastname: Javan
authors.forename: Xiu Quan
authors.initials: XQ
authors.lastname: Zhang
authors.forename: Craig H
authors.initials: CH
authors.lastname: Selzman
mesh_terms: D000222:Adaptation, Physiological / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D004195:Disease Models, Animal; D004452:Echocardiography; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017379:Hypertrophy, Left Ventricular / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000517:prevention & control*; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000201:enzymology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D051996:Transcription Factor RelA / Q000378:metabolism; D020257:Ventricular Remodeling / Q000187:drug effects / Q000502:physiology*
chemical_list: D004791:Enzyme Inhibitors; D051996:Transcription Factor RelA; D051550:I-kappa B Kinase; C496562:Ikbkb protein, mouse