Reduced cardiac remodelling and prevention of glutathione deficiency after omega-3 supplementation in chronic heart failure.
n-3 polyunsaturated fatty acids (omega-3) supplementation is associated with reduced cardiovascular mortality and post-infarction death. However, the impact of omega-3 supplementation in congestive heart failure (CHF) is still unknown. This study assesses the effects of omega-3 supplementation on left ventricular (LV) function and remodelling. We assessed, in rats with CHF induced by left coronary ligation, the effects of a 1-week and a 12-week supplementation with omega-3 (450 mg/kg per day) on LV hemodynamics, function and structure. Chronic omega-3 reduces total peripheral resistance due to an increase in cardiac output without modification of arterial pressure. Only chronic omega-3 reduces LV end-diastolic pressure and LV relaxation constant. Moreover, chronic omega-3 decreases LV systolic and diastolic diameters, LV weight and collagen density. Acute and chronic omega-3 increase LV γ-glutamyl-cysteine synthetase and oppose glutathione deficiency resulting in a reduction of myocardial oxidized glutathione. In experimental CHF, long-term omega-3 supplementation improves LV hemodynamics and function and prevents LV remodelling and glutathione deficiency. The latter might be one of the mechanisms involved, but whether other mechanism, independent of myocardial redox 'status', such as reduced inflammation, are implicated remains to be confirmed.
Fang
Yuehua
Y
INSERM U644, Institut Fédératif de Recherches Multidisciplinaires sur les Peptides n°23, Rouen Institut for Biomedical Research and Inovation, UFR de Médecine et de Pharmacie, 22 Boulevard Gambetta, 76183 Rouen, France.
Favre
Julie
J
Vercauteren
Magalie
M
Laillet
Brigitte
B
Remy-Jouet
Isabelle
I
Skiba
Mohamed
M
Lallemand
Françoise
F
Dehaudt
Cathy
C
Monteil
Christelle
C
Thuillez
Christian
C
Mulder
Paul
P
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects; D019587:Dietary Supplements; D004912:Erythrocytes / Q000378:metabolism; D015525:Fatty Acids, Omega-3 / Q000097:blood / Q000494:pharmacology*; D005721:Glutamate-Cysteine Ligase / Q000378:metabolism; D005978:Glutathione / Q000172:deficiency* / Q000378:metabolism*; D006321:Heart / Q000187:drug effects; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D006439:Hemodynamics / Q000187:drug effects; D008099:Liver / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D014655:Vascular Resistance / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects*
D015525:Fatty Acids, Omega-3; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione