title: Acute administration of n-3 rich triglyceride emulsions provides cardioprotection in murine models after ischemia-reperfusion.
abstract: Dietary n-3 fatty acids (FAs) may reduce cardiovascular disease risk. We questioned whether acute administration of n-3 rich triglyceride (TG) emulsions could preserve cardiac function and decrease injury after ischemia/reperfusion (I/R) insult. We used two different experimental models: in vivo, C57BL/6 mice were exposed to acute occlusion of the left anterior descending coronary artery (LAD), and ex-vivo, C57BL/6 murine hearts were perfused using Langendorff technique (LT). In the LAD model, mice treated with n-3 TG emulsion (1.5 g/kg body weight), immediately after ischemia and 1 h later during reperfusion, significantly reduced infarct size and maintained cardiac function (p<0.05). In the LT model, administration of n-3 TG emulsion (300 mg TG/100 ml) during reperfusion significantly improved functional recovery (p<0.05). In both models, lactate dehydrogenase (LDH) levels, as a marker of injury, were significantly reduced by n-3 TG emulsion. To investigate the mechanisms by which n-3 FAs protects hearts from I/R injury, we investigated changes in key pathways linked to cardioprotection. In the ex-vivo model, we showed that n-3 FAs increased phosphorylation of AKT and GSK3β proteins (p<0.05). Acute n-3 TG emulsion treatment also increased Bcl-2 protein level and reduced an autophagy marker, Beclin-1 (p<0.05). Additionally, cardioprotection by n-3 TG emulsion was linked to changes in PPARγ protein expression (p<0.05). Rosiglitazone and p-AKT inhibitor counteracted the positive effect of n-3 TG; GSK3β inhibitor plus n-3 TG significantly inhibited LDH release. We conclude that acute n-3 TG injection during reperfusion provides cardioprotection. This may prove to be a novel acute adjunctive reperfusion therapy after treating patients with myocardial infarction.
authors.affiliation: Institute of Human Nutrition, College of Physicians and Surgeons, Columbia University, New York, New York, United States of America; Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, New York, United States of America.
authors.forename: Hylde
authors.initials: H
authors.lastname: Zirpoli
authors.affiliation: Institute of Human Nutrition, College of Physicians and Surgeons, Columbia University, New York, New York, United States of America; Department of Medicine, New York University School of Medicine, New York, New York, United States of America.
authors.forename: Mariane
authors.initials: M
authors.lastname: Abdillahi
authors.affiliation: Department of Medicine, New York University School of Medicine, New York, New York, United States of America.
authors.forename: Nosirudeen
authors.initials: N
authors.lastname: Quadri
authors.affiliation: Department of Medicine, New York University School of Medicine, New York, New York, United States of America.
authors.forename: Radha
authors.initials: R
authors.lastname: Ananthakrishnan
authors.affiliation: Department of Medicine, New York University School of Medicine, New York, New York, United States of America.
authors.forename: Lingjie
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Medicine, New York University School of Medicine, New York, New York, United States of America.
authors.forename: Rosa
authors.initials: R
authors.lastname: Rosario
authors.affiliation: Department of Medicine, New York University School of Medicine, New York, New York, United States of America.
authors.forename: Zhengbin
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Institute of Human Nutrition, College of Physicians and Surgeons, Columbia University, New York, New York, United States of America; Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, New York, United States of America.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Deckelbaum
authors.affiliation: Department of Medicine, New York University School of Medicine, New York, New York, United States of America.
authors.forename: Ravichandran
authors.initials: R
authors.lastname: Ramasamy
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D000071186:Beclin-1; D002867:Chromones / Q000494:pharmacology; D004195:Disease Models, Animal; D004452:Echocardiography; D004655:Emulsions / Q000737:chemistry*; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology / Q000627:therapeutic use*; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008301:Maleimides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009025:Morpholines / Q000494:pharmacology; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000517:prevention & control*; D047495:PPAR gamma / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; C115010:Becn1 protein, mouse; D002867:Chromones; D004655:Emulsions; D015525:Fatty Acids, Omega-3; D007211:Indoles; D008301:Maleimides; D009025:Morpholines; D047495:PPAR gamma; D019253:Proto-Oncogene Proteins c-bcl-2; C417521:SB 216763; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3