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Articles

Apoptosis in Human Acute Myocardial Infarction

Antti Saraste, MB; Kari Pulkki, MD; Markku Kallajoki, MD; Kenth Henriksen, MB; Martti Parvinen, MD; Liisa-Maria Voipio-Pulkki, MD

the Departments of Anatomy (A.S., K.H., M.P.), Clinical Chemistry (K.P.), Pathology (M.K.), and Medicine (A.S., L.-M.V.-P.), University of Turku, Kiinamyllynkatu 4-8, Finland.

Correspondence to Liisa-Maria Voipio-Pulkki, MD, Department of Medicine, University of Turku, FIN-20520 Turku, Finland. E-mail liisa-maria.voipio-pulkki{at}utu.fi

Background After reopening of the infarct-related coronary artery, cardiomyocytes continue to die during reperfusion. The mechanisms of cell death have been subject to debate. We studied whether an apoptotic type of cell death occurs in human acute myocardial infarction (AMI).

Methods and Results We studied myocardial samples of eight patients who died of AMI and had patent infarct-related arteries at autopsy. Six of the patients had received initially successful thrombolysis. Extensive formation of DNA strand breaks, the typical biochemical feature of apoptosis, was detected with the use of the in situ DNA end-labeling method. Apoptotic cardiomyocytes were observed particularly in the border zones of histologically infarcted myocardium, whereas very few apoptotic cells were present in the remote noninfarcted myocardium. Internucleosomal fragmentation was confirmed by agarose gel electrophoresis of DNA isolated from the representative myocardial areas.

Conclusions This study provides evidence that in addition to overt necrosis, a subset of myocytes undergo apoptosis during ischemia-reperfusion injury. Apoptosis may provide a new target for cardioprotection during evolving AMI in humans.


Key Words: apoptosis • myocardial infarction • reperfusion • ischemia • thrombolysis




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Cardiovasc Res, August 15, 2002; 55(3): 456 - 465.
[Abstract] [Full Text] [PDF]


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Eur Heart JHome page
G.D. Dispersyn, L. Mesotten, B. Meuris, A. Maes, L. Mortelmans, W. Flameng, F. Ramaekers, and M. Borgers
Dissociation of cardiomyocyte apoptosis and dedifferentiation in infarct border zones
Eur. Heart J., June 1, 2002; 23(11): 849 - 857.
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HeartHome page
M. R Bennett
APOPTOSIS IN THE CARDIOVASCULAR SYSTEM
Heart, May 1, 2002; 87(5): 480 - 487.
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Ann. Thorac. Surg.Home page
J. P. Schmitt, J. Schroder, H. Schunkert, D. E. Birnbaum, and H. Aebert
Role of apoptosis in myocardial stunning after open heart surgery
Ann. Thorac. Surg., April 1, 2002; 73(4): 1229 - 1235.
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Am. J. Physiol. Heart Circ. Physiol.Home page
H. Liu, H. Y. Zhang, X. Zhu, Z. Shao, and Z. Yao
Preconditioning blocks cardiocyte apoptosis: role of KATP channels and PKC-epsilon
Am J Physiol Heart Circ Physiol, April 1, 2002; 282(4): H1380 - H1386.
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J Am Coll CardiolHome page
M. Shimizu, K. Fukuo, S. Nagata, T. Suhara, M. Okuro, K. Fujii, Y. Higashino, M. Mogi, Y. Hatanaka, and T. Ogihara
Increased plasma levels of the soluble form of fas ligand in patients with acute myocardial infarction and unstable angina pectoris
J. Am. Coll. Cardiol., February 20, 2002; 39(4): 585 - 590.
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FASEB J.Home page
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.
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Am. J. Physiol. Heart Circ. Physiol.Home page
Y. Shizukuda and P. M. Buttrick
Protein kinase C-zeta modulates thromboxane A2-mediated apoptosis in adult ventricular myocytes via Akt
Am J Physiol Heart Circ Physiol, January 1, 2002; 282(1): H320 - H327.
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Cardiovasc ResHome page
M. Leicht, W. Briest, A. Holzl, and H.-G. Zimmer
Serum depletion induces cell loss of rat cardiac fibroblasts and increased expression of extracellular matrix proteins in surviving cells
Cardiovasc Res, December 1, 2001; 52(3): 429 - 437.
[Abstract] [Full Text] [PDF]


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Journals of Gerontology Series A: Biological Sciences and Medical SciencesHome page
Z. Mallat, P. Fornes, R. Costagliola, B. Esposito, J. Belmin, D. Lecomte, and A. Tedgui
Age and Gender Effects on Cardiomyocyte Apoptosis in the Normal Human Heart
J. Gerontol. A Biol. Sci. Med. Sci., November 1, 2001; 56(11): M719 - 723.
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Am. J. Physiol. Heart Circ. Physiol.Home page
J. Shiraishi, T. Tatsumi, N. Keira, K. Akashi, A. Mano, S. Yamanaka, S. Matoba, J. Asayama, T. Yaoi, S. Fushiki, et al.
Important role of energy-dependent mitochondrial pathways in cultured rat cardiac myocyte apoptosis
Am J Physiol Heart Circ Physiol, October 1, 2001; 281(4): H1637 - H1647.
[Abstract] [Full Text] [PDF]


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HeartHome page
D Tousoulis, G J Davies, C Tentolouris, G Goumas, C Stefanadis, and P Toutouzas
Vasomotor effects of L- and D-arginine in stenotic atheromatous coronary plaque
Heart, September 1, 2001; 86(3): 296 - 301.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Heart Circ. Physiol.Home page
H. Liu, B. C. McPherson, and Z. Yao
Preconditioning attenuates apoptosis and necrosis: role of protein kinase C{epsilon} and -{delta} isoforms
Am J Physiol Heart Circ Physiol, July 1, 2001; 281(1): H404 - H410.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Heart Circ. Physiol.Home page
E. Palojoki, A. Saraste, A. Eriksson, K. Pulkki, M. Kallajoki, L.-M. Voipio-Pulkki, and I. Tikkanen
Cardiomyocyte apoptosis and ventricular remodeling after myocardial infarction in rats
Am J Physiol Heart Circ Physiol, June 1, 2001; 280(6): H2726 - H2731.
[Abstract] [Full Text] [PDF]


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Cardiovasc ResHome page
M. Palmen, M.J.A.P. Daemen, R. Bronsaer, W.R.M. Dassen, H.R. Zandbergen, M. Kockx, J.F.M. Smits, R. van der Zee, and P.A. Doevendans
Cardiac remodeling after myocardial infarction is impaired in IGF-1 deficient mice
Cardiovasc Res, June 1, 2001; 50(3): 516 - 524.
[Abstract] [Full Text] [PDF]


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PerfusionHome page
A. E Basile-Borgia and V. C Ware
Life and death of a cardiac myocyte: principles of cellular biology
Perfusion, May 1, 2001; 16(3): 229 - 241.
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PhysiologyHome page
G. D. Dispersyn and M. Borgers
Apoptosis in the Heart: About Programmed Cell Death and Survival
Physiology, February 1, 2001; 16(1): 41 - 47.
[Abstract] [Full Text] [PDF]


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HeartHome page
D Tousoulis, C Tentolouris, T Crake, G Goumas, C Stefanadis, P Toutouzas, and G Davies
Complex stenosis morphology and vasomotor responses to inhibition of nitric oxide synthesis
Heart, November 1, 2000; 84(5): 529 - 534.
[Abstract] [Full Text]


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Cardiovasc ResHome page
K. Yasui, K. Kada, M. Hojo, J.-K. Lee, K. Kamiya, J. Toyama, T. Opthof, and I. Kodama
Cell-to-cell interaction prevents cell death in cultured neonatal rat ventricular myocytes
Cardiovasc Res, October 1, 2000; 48(1): 68 - 76.
[Abstract] [Full Text] [PDF]


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Cardiovasc ResHome page
T. Imanishi, C. E. Murry, H. Reinecke, T. Hano, I. Nishio, W.C. Liles, L. Hofsta, K. Kim, K. D. O'Brien, S. M. Schwartz, et al.
Cellular FLIP is expressed in cardiomyocytes and down-regulated in TUNEL-positive grafted cardiac tissues
Cardiovasc Res, October 1, 2000; 48(1): 101 - 110.
[Abstract] [Full Text] [PDF]


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Eur Heart JHome page
Myocardial
Myocardial infarction redefined--A consensus document of The Joint European Society of Cardiology/American College of Cardiology Committee for the Redefinition of Myocardial Infarction
Eur. Heart J., September 2, 2000; 21(18): 1502 - 1513.
[Abstract] [PDF]


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CirculationHome page
I. Jeremias, C. Kupatt, A. Martin-Villalba, H. Habazettl, J. Schenkel, P. Boekstegers, and K. M. Debatin
Involvement of CD95/Apo1/Fas in Cell Death After Myocardial Ischemia
Circulation, August 22, 2000; 102(8): 915 - 920.
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Circ. Res.Home page
P. M. Kang and S. Izumo
Apoptosis and Heart Failure : A Critical Review of the Literature
Circ. Res., June 9, 2000; 86(11): 1107 - 1113.
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J Am Coll CardiolHome page
N. Latif, M. A. Khan, E. Birks, A. O'Farrell, J. Westbrook, M. J. Dunn, and M. H. Yacoub
Upregulation of the Bcl-2 family of proteins in end stage heart failure
J. Am. Coll. Cardiol., June 1, 2000; 35(7): 1769 - 1777.
[Abstract] [Full Text] [PDF]


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CirculationHome page
T. N. James
Homage to James B. Herrick: A Contemporary Look at Myocardial Infarction and at Sickle-Cell Heart Disease : The 32nd Annual Herrick Lecture of the Council on Clinical Cardiology of the American Heart Association
Circulation, April 18, 2000; 101(15): 1874 - 1887.
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Cancer Res.Home page
O. J. Arola, A. Saraste, K. Pulkki, M. Kallajoki, M. Parvinen, and L.-M. Voipio-Pulkki
Acute Doxorubicin Cardiotoxicity Involves Cardiomyocyte Apoptosis
Cancer Res., April 1, 2000; 60(7): 1789 - 1792.
[Abstract] [Full Text]


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Cardiovasc ResHome page
H. Spitznagel, O. Chung, Q.-G. Xia, B. Rossius, S. Illner, G. Jahnichen, S. Sandmann, A. Reinecke, M. J.A.P. Daemen, and T. Unger
Cardioprotective effects of the Na+/H+-exchange inhibitor cariporide in infarct-induced heart failure
Cardiovasc Res, April 1, 2000; 46(1): 102 - 110.
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Circ. Res.Home page
J.-i. Abe, C. P. Baines, and B. C. Berk
Role of Mitogen-Activated Protein Kinases in Ischemia and Reperfusion Injury : The Good and the Bad
Circ. Res., March 31, 2000; 86(6): 607 - 609.
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Circ. Res.Home page
A. Haunstetter and S. Izumo
Toward Antiapoptosis as a New Treatment Modality
Circ. Res., March 3, 2000; 86(4): 371 - 376.
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Circ. Res.Home page
L. J. De Windt, H. W. Lim, T. Taigen, D. Wencker, G. Condorelli, G. W. Dorn II, R. N. Kitsis, and J. D. Molkentin
Calcineurin-Mediated Hypertrophy Protects Cardiomyocytes From Apoptosis In Vitro and In Vivo : An Apoptosis-Independent Model of Dilated Heart Failure
Circ. Res., February 18, 2000; 86(3): 255 - 263.
[Abstract] [Full Text] [PDF]


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Cardiovasc ResHome page
A. Saraste and K. Pulkki
Morphologic and biochemical hallmarks of apoptosis
Cardiovasc Res, February 1, 2000; 45(3): 528 - 537.
[Abstract] [Full Text] [PDF]


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Cardiovasc ResHome page
H. Yaoita, K. Ogawa, K. Maehara, and Y. Maruyama
Apoptosis in relevant clinical situations: contribution of apoptosis in myocardial infarction
Cardiovasc Res, February 1, 2000; 45(3): 630 - 641.
[Abstract] [Full Text] [PDF]


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Cardiovasc ResHome page
Z.-Q. Zhao, M. Nakamura, N.-P. Wang, J. N. Wilcox, S. Shearer, R. S. Ronson, R. A. Guyton, and J. Vinten-Johansen
Reperfusion induces myocardial apoptotic cell death
Cardiovasc Res, February 1, 2000; 45(3): 651 - 660.
[Abstract] [Full Text] [PDF]


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Cardiovasc ResHome page
G. D. Dispersyn, M. Borgers, and W. Flameng
Apoptosis in chronic hibernating myocardium: sleeping to death?
Cardiovasc Res, February 1, 2000; 45(3): 696 - 703.
[Abstract] [Full Text] [PDF]


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Cardiovasc ResHome page
H. N. Sabbah
Apoptotic cell death in heart failure
Cardiovasc Res, February 1, 2000; 45(3): 704 - 712.
[Full Text] [PDF]