TY - JOUR
T1 - Temporal and spatial variations in structural protein expression during the progression from stunned to hibernating myocardium
AU - Thijssen, V L J L
AU - Borgers, M
AU - Lenders, M-H
AU - Ramaekers, F C S
AU - Suzuki, G
AU - Palka, B
AU - Fallavollita, J A
AU - Thomas, S A
AU - Canty, J M
PY - 2004/11/23
Y1 - 2004/11/23
N2 - 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.METHODS AND 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.
AB - 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.METHODS AND 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.
KW - Actinin/biosynthesis
KW - Actins/biosynthesis
KW - Animals
KW - Connectin
KW - Coronary Disease/genetics
KW - Cytoskeletal Proteins/biosynthesis
KW - Desmin/biosynthesis
KW - Desmoplakins
KW - Disease Progression
KW - Fetal Proteins/biosynthesis
KW - Gene Expression Regulation
KW - Lamin Type A/biosynthesis
KW - Lamin Type B/biosynthesis
KW - Muscle Proteins/biosynthesis
KW - Myocardial Ischemia/genetics
KW - Myocardial Stunning/genetics
KW - Pressure
KW - Protein Kinases/biosynthesis
KW - Single-Blind Method
KW - Sus scrofa
U2 - 10.1161/01.CIR.0000147826.13480.99
DO - 10.1161/01.CIR.0000147826.13480.99
M3 - Article
C2 - 15545518
VL - 110
SP - 3313
EP - 3321
JO - Circulation
JF - Circulation
SN - 0009-7322
IS - 21
ER -