© 2000 by European Society of Cardiology
Copyright © 2000, European Society of Cardiology
Reperfusion induces myocardial apoptotic cell death
aDepartment of Surgery, Section of Cardiothoracic Surgery, Emory University School of Medicine, 550 Peachtree St. N.E., Atlanta, GA 30365-2225, USA
bDepartment of Hematology/Oncology, Emory University School of Medicine, Atlanta, GA 30365-2225, USA
* Corresponding author. Tel.: +1-404-686-2511; fax: +1-404-686-4888
Objective: The purpose of the present study was to investigate whether apoptosis is triggered during ischemia (I) and reperfusion (R) and whether I/R-induced apoptosis is correlated with changes in expression of Bcl-2 and Bax. Methods: Anesthetized open-chest dogs were divided into two groups. Group I: 7 h of permanent I without R (PI, n=7); Group II: 60 min I followed by 6 h R (I/R, n=8). Apoptosis was identified as "DNA ladder" by agarose gel electrophoresis or confirmed histologically using the terminal transferase UTP nick end labeling (TUNEL) assay. Results: Collateral myocardial coronary blood flow during I, confirmed by colored microspheres was comparable in both groups. Although PI caused 72±5% infarct size, very few TUNEL-positive cells were detected in the necrotic area (0.2±0.1% of total normal nuclei), consistent with an absence of DNA laddering. In contrast, the appearance of TUNEL-positive cells was significantly displayed after 6 h R in the necrotic area in I/R group (26±4%, P<0.001 vs. PI group), and DNA ladder occurred in all experimental animals, suggesting that myocardial apoptosis is primarily elicited by R. Densitometrically, Western blot analysis showed significant reduction in expression of Bcl-2 (16±1%) and increase in Bax (29±8%) after 6 h R in the necrotic area compared with normal tissue while expression of these two proteins was not changed in the PI group. Polymorphonuclear neutrophil (PMN) accumulation in the necrotic area determined either by immunohistochemistry with anti-CD18 antibody or by myeloperoxidase activity was significantly increased in the I/R group compared to the PI group (358±24 vs. 24±2, mm2 myocardium, P<0.01) and (2.9±0.3 vs. 0.4±0.1, U/100 mg tissue, P<0.01). There was a significant linear relationship between CD18-positive PMNs and TUNEL-positive cells (P<0.05) in the I/R group. Conclusions: These results indicate that (1) PI without R did not induce apoptotic cell death, while two types of cell death, necrosis and apoptosis were found after I/R, (2) the Bcl-2 family may participate in early R-induced myocardial apoptosis, (3) PMN accumulation may play a role in the development of apoptosis.
KEYWORDS Apoptosis; Necrosis; Reperfusion
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|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
J. Pye, F. Ardeshirpour, A. McCain, D. A. Bellinger, E. Merricks, J. Adams, P. J. Elliott, C. Pien, T. H. Fischer, A. S. Baldwin Jr., et al. Proteasome inhibition ablates activation of NF-kappa B in myocardial reperfusion and reduces reperfusion injury Am J Physiol Heart Circ Physiol, March 1, 2003; 284(3): H919 - H926. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P A J Krijnen, R Nijmeijer, C J L M Meijer, C A Visser, C E Hack, and H W M Niessen Apoptosis in myocardial ischaemia and infarction J. Clin. Pathol., November 1, 2002; 55(11): 801 - 811. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Bartunek, M. Vanderheyden, M. W. M. Knaapen, W. Tack, M. M. Kockx, and M. Goethals Deoxyribonucleic acid damage/repairproteins are elevated in the failing human myocardium due to idiopathic dilated cardiomyopathy J. Am. Coll. Cardiol., September 18, 2002; 40(6): 1097 - 1103. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z.-Q. Zhao and J. Vinten-Johansen Myocardial apoptosis and ischemic preconditioning Cardiovasc Res, August 15, 2002; 55(3): 438 - 455. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. GILL, R. MESTRIL, and A. SAMALI Losing heart: the role of apoptosis in heart disease--a novel therapeutic target? FASEB J, February 1, 2002; 16(2): 135 - 146. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Scarabelli, A. Stephanou, N. Rayment, E. Pasini, L. Comini, S. Curello, R. Ferrari, R. Knight, and D. Latchman Apoptosis of Endothelial Cells Precedes Myocyte Cell Apoptosis in Ischemia/Reperfusion Injury Circulation, July 17, 2001; 104(3): 253 - 256. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Taimor Cardiac gap junctions: good or bad? Cardiovasc Res, October 1, 2000; 48(1): 8 - 10. [Full Text] [PDF]
|
|
|
|
|
|
M. Borgers, L.-M. Voipio-Pulkki, and S. Izumo Apoptosis Cardiovasc Res, February 1, 2000; 45(3): 525 - 527. [Full Text] [PDF]
|
|