title: Temporal and spatial variations in structural protein expression during the progression from stunned to hibernating myocardium.
abstract: BACKGROUND
  Dysfunctional and normally perfused remote regions show equal myolysis and glycogen accumulation in pig hibernating myocardium. We tested the hypothesis that these arose secondary to elevations in preload rather than ischemia.
  
  
  RESULTS
  Expression of structural protein (desmin, desmoplakin, titin, cardiotin, alpha-smooth muscle actin, lamin-A/C, and lamin-B2) in viable dysfunctional myocardium was analyzed by immunohistochemistry. We performed blinded analysis of paired dysfunctional left anterior descending coronary artery and normal remote subendocardial samples from stunned (24 hours; n=6), and hibernating (2 weeks; n=6) myocardium versus sham controls pigs (n=7). Within 24 hours, cardiac myocytes globally reexpressed alpha-smooth muscle actin. In stunned myocardium, cardiotin was globally reduced, whereas reductions in desmin were restricted to the dysfunctional region. Alterations progressed with the transition to hibernating myocardium, in which desmin, cardiotin, and titin were globally reduced. A qualitatively similar reorganization of cytoskeletal proteins occurred 3 hours after transient elevation of left ventricular end-diastolic pressure to 33+/-3 mm Hg.
  
  
  CONCLUSIONS
  Qualitative cardiomyocyte remodeling similar to that in humans with chronic hibernation occurs rapidly after a critical coronary stenosis is applied, as well as after transient elevations in left ventricular end-diastolic pressure in the absence of ischemia. Thus, reorganization of cytoskeletal proteins in patients with viable dysfunctional myocardium appears to reflect chronic and/or cyclical elevations in preload associated with episodes of spontaneous regional ischemia.
authors.affiliation: Department of Molecular Cell Biology, Cardiovascular Research Institute Maastricht, University of Maastricht, The Netherlands. v.thijssen@path.unimaas.nl
authors.forename: V L J L
authors.initials: VL
authors.lastname: Thijssen
authors.forename: M
authors.initials: M
authors.lastname: Borgers
authors.forename: M-H
authors.initials: MH
authors.lastname: Lenders
authors.forename: F C S
authors.initials: FC
authors.lastname: Ramaekers
authors.forename: G
authors.initials: G
authors.lastname: Suzuki
authors.forename: B
authors.initials: B
authors.lastname: Palka
authors.forename: J A
authors.initials: JA
authors.lastname: Fallavollita
authors.forename: S A
authors.initials: SA
authors.lastname: Thomas
authors.forename: J M
authors.initials: JM
authors.lastname: Canty
mesh_terms: D000185:Actinin / Q000096:biosynthesis / Q000235:genetics; D000199:Actins / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D064211:Connectin; D003327:Coronary Disease / Q000235:genetics / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000096:biosynthesis* / Q000235:genetics; D003893:Desmin / Q000096:biosynthesis / Q000235:genetics; D051180:Desmoplakins; D018450:Disease Progression; D005326:Fetal Proteins / Q000096:biosynthesis / Q000235:genetics; D005786:Gene Expression Regulation; D034904:Lamin Type A / Q000096:biosynthesis / Q000235:genetics; D034921:Lamin Type B / Q000096:biosynthesis / Q000235:genetics; D009124:Muscle Proteins / Q000096:biosynthesis* / Q000235:genetics; D017202:Myocardial Ischemia / Q000235:genetics / Q000378:metabolism; D017682:Myocardial Stunning / Q000235:genetics* / Q000378:metabolism; D011312:Pressure; D011494:Protein Kinases / Q000096:biosynthesis / Q000235:genetics; D016037:Single-Blind Method; D034421:Sus scrofa
chemical_list: D000199:Actins; D064211:Connectin; D003598:Cytoskeletal Proteins; D003893:Desmin; D051180:Desmoplakins; D005326:Fetal Proteins; D034904:Lamin Type A; D034921:Lamin Type B; D009124:Muscle Proteins; C577285:TTN protein, human; C104594:cardiotin; C440308:lamin C; D000185:Actinin; D011494:Protein Kinases