| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Division of Cardiovascular Medicine, Department of Medicine, Henry Ford Heart and Vascular Institute, Detroit, Michigan 48202
Cardiomyocyte apoptosis or programmed cell death has been shown to occur in end-stage explanted failed human hearts and in dogs with chronic heart failure (HF). We tested the hypothesis that early long-term monotherapy with an angiotensin-converting enzyme (ACE) inhibitor attenuates cardiomyocyte apoptosis in dogs with moderate HF. Left ventricular (LV) dysfunction (ejection fraction 30-40%) was produced in dogs by multiple sequential intracoronary microembolizations. Dogs were randomized to 3 mo of therapy with enalapril (Ena, 10 mg twice daily, n = 7) or to no therapy at all (control, n = 7). After 3 mo of therapy, dogs were euthanized and the hearts removed. Presence of nuclear DNA fragmentation (nDNAf), a marker of apoptosis, was assessed in frozen LV sections using the immunohistochemical deoxynucleotidal transferase-mediated dUTP-digoxigenin nick-end labeling (TUNEL) method. Sections were also stained with ventricular anti-myosin antibody to identify cells of cardiocyte origin. From each dog, 80 fields (×40) were selected at random, 40 from LV regions bordering old infarcts and 40 from LV regions remote from any infarcts, for quantifying the number of cardiomyocyte nDNAf events per 1,000 cardiomyocytes. The average number of cardiomyocyte nDNAf events per 1,000 cardiomyocytes was significantly lower in Ena-treated dogs compared with controls (0.81 ± 0.13 vs. 2.65 ± 0.81, P < 0.029). This difference was due to a significantly lower incidence of cardiomyocyte nDNAf events in LV regions bordering scarred tissue (infarcts) in Ena-treated dogs compared with controls. We conclude that early long-term Ena therapy attenuates cardiomyocyte apoptosis in dogs with moderate HF. Attenuation of cardiomyocyte apoptosis may be one mechanism by which ACE inhibitors preserve global LV function in HF.
ventricular function; angiotensin-converting enzyme inhibitors; programmed cell death
This article has been cited by other articles:
|
|
 |
|
  M. Park, Y.-T. Shen, V. Gaussin, G. R. Heyndrickx, J. Bartunek, R. R. G. Resuello, F. F. Natividad, R. N. Kitsis, D. E. Vatner, and S. F. Vatner Apoptosis predominates in nonmyocytes in heart failure Am J Physiol Heart Circ Physiol, August 1, 2009; 297(2): H785 - H791. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. C. Okere, M. P. Chandler, T. A. McElfresh, J. H. Rennison, V. Sharov, H. N. Sabbah, K.-Y. Tserng, B. D. Hoit, P. Ernsberger, M. E. Young, et al. Differential effects of saturated and unsaturated fatty acid diets on cardiomyocyte apoptosis, adipose distribution, and serum leptin Am J Physiol Heart Circ Physiol, July 1, 2006; 291(1): H38 - H44. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Todor, V. G. Sharov, E. J. Tanhehco, N. Silverman, A. Bernabei, and H. N. Sabbah Hypoxia-induced cleavage of caspase-3 and DFF45/ICAD in human failed cardiomyocytes Am J Physiol Heart Circ Physiol, September 1, 2002; 283(3): H990 - H995. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 L. Barlucchi, A. Leri, D. E. Dostal, F. Fiordaliso, H. Tada, T. H. Hintze, J. Kajstura, B. Nadal-Ginard, and P. Anversa Canine Ventricular Myocytes Possess a Renin-Angiotensin System That Is Upregulated With Heart Failure Circ. Res., February 16, 2001; 88(3): 298 - 304. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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. [Full Text] [PDF]
|
|
|
|
|
|
S. Guerra, A. Leri, X. Wang, N. Finato, C. Di Loreto, C. A. Beltrami, J. Kajstura, and P. Anversa Myocyte Death in the Failing Human Heart Is Gender Dependent Circ. Res., October 29, 1999; 85(9): 856 - 866. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B.-S. Tea, T.-V. Dam, P. Moreau, P. Hamet, and D. deBlois Apoptosis During Regression of Cardiac Hypertrophy in Spontaneously Hypertensive Rats : Temporal Regulation and Spatial Heterogeneity Hypertension, August 1, 1999; 34(2): 229 - 235. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. N. Diep, M. El Mabrouk, P. Yue, and E. L. Schiffrin Effect of AT1 receptor blockade on cardiac apoptosis in angiotensin II-induced hypertension Am J Physiol Heart Circ Physiol, May 1, 2002; 282(5): H1635 - H1641. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
