The Effects of Aging on Apoptosis Following Myocardial Infarction

被引：26

作者：

Boyle, Andrew J. ^{[1
,2
]}

Hwang, Joy ^{[1
]}

Ye, Jianqin ^{[1
,2
]}

Shih, Henry ^{[1
]}

Jun, Kristine ^{[1
]}

Zhang, Yan ^{[1
]}

Fang, Qizhi ^{[1
,2
]}

Sievers, Richard ^{[1
]}

Yeghiazarians, Yerem ^{[1
,2
]}

Lee, Randall J. ^{[1
,2
,3
]}

机构：

[1] Univ Calif San Francisco, Dept Med, Div Cardiol, San Francisco, CA 94143 USA

[2] Univ Calif San Francisco, Edyth & Eli Broad Ctr Regenerat Med & Stem Cell R, San Francisco, CA 94143 USA

[3] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA

来源：

CARDIOVASCULAR THERAPEUTICS | 2013年 / 31卷 / 06期

关键词：

Aging; Apoptosis; Cardiomyocyte; Heart failure; Ventricular remodeling; CELL THERAPY; PROGENITOR CELLS; HEART-FAILURE; IMPROVEMENT; INHIBITION; MORTALITY; IMPAIRS; MODEL; MICE;

D O I：

10.1111/1755-5922.12043

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

BackgroundAging is associated with higher incidence of heart failure and death following myocardial infarction (MI). The molecular and cellular changes that lead to these worse outcomes are not known. Methods and ResultsYoung and aging mice underwent induction of MI by LAD ligation. There was a significant increase in mortality in the aging mice. Neither the young nor aging hearts after MI had inducible ventricular tachycardia. Cardiomyocyte apoptosis increases early after MI in young and aging mice, but to a much greater degree in the aging mice. Caspase inhibition with Ac-DEVD-CHO resulted in a 61% reduction in activated caspase-3 and an 84% reduction in apoptosis in cardiomyocytes in young mice (P<0.05), but not in aging mice. Gene pathway profiling demonstrated activation of both the caspase and Map3k1/Mapk10 pathways in aging mice following MI, which may contribute to their resistance to caspase inhibition. ConclusionsAging hearts activate distinct apoptotic pathways have more cardiomyocyte apoptosis and are resistant to antiapoptotic therapies following MI. Novel or combination approaches may be required to improve outcomes in aging patients following MI.

引用

页码：E102 / E110

页数：9

共 24 条

[1]

[Anonymous], INC PREV 2006 CHART

[2]

Additive effects of endothelial progenitor cells combined with ACE inhibition and β-blockade on left ventricular function following acute myocardial infarction [J].

Boyle, AJ ;

Schuster, M ;

Witkowski, P ;

Xiang, GS ;

Seki, T ;

Way, K ;

Itescu, S .

JOURNAL OF THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM, 2005, 6 (01) :33-37

[3]

Cardiomyopathy of aging in the mammalian heart is characterized by myocardial hypertrophy, fibrosis and a predisposition towards cardiomyocyte apoptosis and autophagy [J].

Boyle, Andrew J. ;

Shih, Henry ;

Hwang, Joy ;

Ye, Jianqin ;

Lee, Brian ;

Zhang, Yan ;

Kwon, David ;

Jun, Kristine ;

Zheng, Daiwei ;

Sievers, Rich ;

Angeli, Franca ;

Yeghiazarians, Yerem ;

Lee, Randall .

EXPERIMENTAL GERONTOLOGY, 2011, 46 (07) :549-559

[4]

Bujak, Marcin ;

Kweon, Hyuk Jung ;

Chatila, Khaled ;

Li, Na ;

Taffet, George ;

Frangogiannis, Nikolaos G. .

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2008, 51 (14) :1384-1392

[5]

GenMAPP, a new tool for viewing and analyzing microarray data on biological pathways [J].

Dahlquist, KD ;

Salomonis, N ;

Vranizan, K ;

Lawlor, SC ;

Conklin, BR .

NATURE GENETICS, 2002, 31 (01) :19-20

[6]

Heart function and molecular biological parameters are comparable in young adult and aged rats after chronic myocardial infarction [J].

Deten, A ;

Marx, G ;

Briest, W ;

Volz, HC ;

Zimmer, HG .

CARDIOVASCULAR RESEARCH, 2005, 66 (02) :364-373

[7]

Declining In-Hospital Mortality and Increasing Heart Failure Incidence in Elderly Patients With First Myocardial Infarction [J].

Ezekowitz, Justin A. ;

Kaul, Padma ;

Bakal, Jeffery A. ;

Armstrong, Paul W. ;

Welsh, Robert C. ;

McAlister, Finlay A. .

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2009, 53 (01) :13-20

[8]

Bioconductor: open software development for computational biology and bioinformatics [J].

Gentleman, RC ;

Carey, VJ ;

Bates, DM ;

Bolstad, B ;

Dettling, M ;

Dudoit, S ;

Ellis, B ;

Gautier, L ;

Ge, YC ;

Gentry, J ;

Hornik, K ;

Hothorn, T ;

Huber, W ;

Iacus, S ;

Irizarry, R ;

Leisch, F ;

Li, C ;

Maechler, M ;

Rossini, AJ ;

Sawitzki, G ;

Smith, C ;

Smyth, G ;

Tierney, L ;

Yang, JYH ;

Zhang, JH .

GENOME BIOLOGY, 2004, 5 (10)

[9]

Heart failure and greater infarct expansion in middle-aged mice: a relevant model for postinfarction failure [J].

Gould, KE ;

Taffet, GE ;

Michael, LH ;

Christie, RM ;

Konkol, DL ;

Pocius, JS ;

Zachariah, JP ;

Chaupin, DF ;

Daniel, SL ;

Sandusky, GE ;

Hartley, CJ ;

Entman, ML .

AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2002, 282 (02) :H615-H621

[10]

Bone Marrow Mesenchymal Stem Cells Stimulate Cardiac Stem Cell Proliferation and Differentiation [J].

Hatzistergos, Konstantinos E. ;

Quevedo, Henry ;

Oskouei, Behzad N. ;

Hu, Qinghua ;

Feigenbaum, Gary S. ;

Margitich, Irene S. ;

Mazhari, Ramesh ;

Boyle, Andrew J. ;

Zambrano, Juan P. ;

Rodriguez, Jose E. ;

Dulce, Raul ;

Pattany, Pradip M. ;

Valdes, David ;

Revilla, Concepcion ;

Heldman, Alan W. ;

McNiece, Ian ;

Hare, Joshua M. .

CIRCULATION RESEARCH, 2010, 107 (07) :913-+

← 1 2 3 →