Infusion of docosahexaenoic acid protects against myocardial infarction.
Most of the cardioprotective effects of long-chain omega 3 fatty acids, namely docosahexaenoic (DHA; 22:6n-3) and eicosapentaenoic (EPA; 20:5n-3), are due to their hypotriglyceridemic and anti-inflammatory effects, which lower the risk for cardiovascular disease and myocardial infarction. Little is known on the direct preventive activities of DHA and EPA on heart function. In isolated hearts, we studied (1) whether infused DHA is able to protect the heart from ischemia/reperfusion damage and (2) the role played by Notch-mediated signal transduction pathways in myocardial infarction. Perfusion with DHA before and before/after induction of ischemia reperfusion significantly diminished cardiac damage and afforded antioxidant protection. Mechanistically, infusion of DHA before and before/after the induction of ischemia differentially modulated the expression of Notch2 and 3 target genes. In particular, DHA increased the expression of Hey1 when infused pre- and pre/post-ischemia; Jagged 1 and the Notch2 receptors increased with DHA pre-ischemia, but not pre/post; Notch2 and 3 receptors as well as Delta increased following DHA administration pre- and (especially) pre/post-ischemia. In conclusion, while the precise nature of the Notch-mediated protection from ischemia/reperfusion afforded by DHA is as yet to be fully elucidated, our data add to the growing body of literature that indicates how systemic administration of DHA provides cardiovascular protection.
Université Pierre et Marie Curie, Paris, France.
D
D
Richard
EA3801 HERVI (Hémostase et Remodelage Vasculaire post-Ischémique), Université de Reims Champagne-Ardenne, France.
F
F
Oszust
EA 4691 BiOs (Biomatériaux et inflammation en site Osseux), Université de Reims Champagne-Ardenne, France.
C
C
Guillaume
EA3801 HERVI (Hémostase et Remodelage Vasculaire post-Ischémique), Université de Reims Champagne-Ardenne, France.
H
H
Millart
EA 4691 BiOs (Biomatériaux et inflammation en site Osseux), Université de Reims Champagne-Ardenne, France.
D
D
Laurent-Maquin
Unité de Signalisation Moléculaire et Activation Cellulaire, Institut Pasteur, Paris, France.
C
C
Brou
Université Pierre et Marie Curie, Paris, France.
P
P
Bausero
IMDEA-Food, CEI UAM+CSIC, C/Faraday 7, 28049 Madrid, Spain. Electronic address: francesco.visioli@imdea.org.
F
F
Visioli
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000473:pathology; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D051880:Receptors, Notch / Q000378:metabolism; D015398:Signal Transduction; D016276:Ventricular Function / Q000187:drug effects
D000975:Antioxidants; D002316:Cardiotonic Agents; D051880:Receptors, Notch; D004281:Docosahexaenoic Acids
Cardioprotection; Docosahexaenoic acid; Ischemia; Notch; Reperfusion