CLINICAL STUDY
Physical training in patients with chronic heart failure enhances the expression of genes encoding antioxidative enzymes
Pierre V. Ennezat, MD*   ,
Slawomir L. Malendowicz, MD* ,
Marco Testa, MD, PhD*,
Paolo C. Colombo, MD*,
Alain Cohen-Solal, MD,
Todd Evans, PhD and
Thierry H. LeJemtel, MD*
* Department of Medicine, Division of Cardiology, Albert Einstein College of Medicine, Bronx, New York, USA
Department of Developmental and Molecular Biology, the Albert Einstein College of Medicine, Bronx, New York, USA
Division of Cardiology, Beaujon Hospital, Clichy, France
Manuscript received May 23, 2000;
revised manuscript received March 2, 2001,
accepted March 23, 2001.
Reprint requests and correspondence: Dr. Thierry H. LeJemtel, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Forcheimer. G-44, Bronx, New York 10461
lejemtel{at}aecom.yu.edu
OBJECTIVES
We sought to determine whether the benefit of training for vasodilation in the skeletal muscle vasculature of patients with chronic heart failure (CHF) is likely to be caused at the molecular level primarily by increased nitric oxide (NO) production or decreased inactivation of NO.
BACKGROUND
Physical training reverses endothelium dysfunction in patients with CHF, mediated by increased NO bioactivity. Some animal studies support a mechanism whereby training results in increased vascular NO levels by sustained transcriptional activation of the endothelial NO synthase (eNOS) gene, presumably due to shear stress. The mechanism has not been addressed in patients with CHF.
METHODS
The steady state transcript levels for eNOS and two other shear stress regulated genes (angiotensin-converting enzyme [ACE] and prostacyclin synthase [PGI2S]) were measured in samples of skeletal muscle from patients with CHF before and after 12 weeks of training. Transcript levels were measured in the same samples for two genes encoding antioxidant enzymes, copper zinc superoxide dismutase (Cu/Zn SOD) and glutathione peroxidase (GSH-Px). Untrained patients served as controls.
RESULTS
As expected, training significantly enhanced peak oxygen uptake in the patients with CHF. Training did not increase steady-state transcript levels for eNOS, ACE or PGI2S. In striking contrast, training increased the expression of the antioxidative enzyme genes by approximately 100%.
CONCLUSIONS
Our results do not support a model of benefit from training by increased eNOS expression. However, the data are entirely consistent with the alternative hypothesis, that reduced oxidative stress may account for the increase in vascular NO-mediated vasodilation. Insight into the mechanism may be relevant when considering therapies for exercise-intolerant patients with CHF.
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Abbreviations and Acronyms
| | ACE | = angiotensin-converting enzyme | | cDNA | = complementary DNA | | CHF | = chronic heart failure | | Cu/Zn SOD | = copper zinc superoxide dismutase | | eNOS | = endothelial nitric oxide synthase | | GSH-Px | = glutathione peroxidase | | mRNA | = messenger RNA | | NO | = nitric oxide | | NT | = nontrained group | | PCR | = polymerase chain reaction | | PGI2S | = prostacyclin synthase | | RT | = reverse transcription | | RT/PCR | = reverse transcription polymerase chain reaction | | T | = trained group | | VWF | = Von Willebrand factor |
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