Laura A Scrimgeour1, Brittany A Potz1, Nassrene Y Elmadhun1, Louis M Chu1, Frank W Sellke2. 1. Division of Cardiothoracic Surgery, Department of Surgery, Lifespan Hospitals, Warren Alpert School of Medicine, Brown University, Providence, RI. 2. Division of Cardiothoracic Surgery, Department of Surgery, Lifespan Hospitals, Warren Alpert School of Medicine, Brown University, Providence, RI. Electronic address: fsellke@lifespan.org.
Abstract
BACKGROUND: Moderate alcohol consumption is cardioprotective but the mechanism of action remains unclear. Nuclear factor κ-B regulates the expression of genes involved in inflammation, stress, and apoptosis. We used a swine model of diet-induced metabolic syndrome to investigate the effects of red wine and vodka on nuclear factor κ-B signaling and cytokine activity in chronically ischemic myocardium. METHODS: Yorkshire swine were given a high-fat diet for 4 weeks; an ameroid constrictor was then placed on the left circumflex artery. The high-fat diet was continued and the swine were divided into 3 groups for 7 weeks: hypercholesterolemic diet alone (control, n = 8), hypercholesterolemic diet with vodka (vodka, n = 8), and hypercholesterolemic diet with wine (wine, n = 8). Ischemic myocardium was analyzed by Western blot and cytokine array. RESULTS: Administration of alcohol was associated with decreased expression of inhibitor of κ-B kinase complex α, inhibitor of κ-B kinase complex β, and phosphorylated inhibitor of κ-B β in the ischemic myocardium compared with the control group. Alcohol administration demonstrated an increase in nuclear factor κ-B in the ischemic myocardium. Both wine and vodka demonstrated a significant decrease in leptin, interleukin-1α, IL-13, IL-15, and interferon-γ. Vodka demonstrated a significant decrease in phosphorylated BCL-2 and caspase-9. CONCLUSION: In ischemic myocardium, alcohol modulates the nuclear factor κ-B pathway, which may contribute to the adaptive response of tissues to the stress of ischemia. Furthermore, both wine and vodka decreased multiple proinflammatory cytokines. This study provides a mechanism by which alcohol may be cardioprotective in ischemic myocardium.
BACKGROUND: Moderate alcohol consumption is cardioprotective but the mechanism of action remains unclear. Nuclear factor κ-B regulates the expression of genes involved in inflammation, stress, and apoptosis. We used a swine model of diet-induced metabolic syndrome to investigate the effects of red wine and vodka on nuclear factor κ-B signaling and cytokine activity in chronically ischemic myocardium. METHODS: Yorkshire swine were given a high-fat diet for 4 weeks; an ameroid constrictor was then placed on the left circumflex artery. The high-fat diet was continued and the swine were divided into 3 groups for 7 weeks: hypercholesterolemic diet alone (control, n = 8), hypercholesterolemic diet with vodka (vodka, n = 8), and hypercholesterolemic diet with wine (wine, n = 8). Ischemic myocardium was analyzed by Western blot and cytokine array. RESULTS: Administration of alcohol was associated with decreased expression of inhibitor of κ-B kinase complex α, inhibitor of κ-B kinase complex β, and phosphorylated inhibitor of κ-B β in the ischemic myocardium compared with the control group. Alcohol administration demonstrated an increase in nuclear factor κ-B in the ischemic myocardium. Both wine and vodka demonstrated a significant decrease in leptin, interleukin-1α, IL-13, IL-15, and interferon-γ. Vodka demonstrated a significant decrease in phosphorylated BCL-2 and caspase-9. CONCLUSION: In ischemic myocardium, alcohol modulates the nuclear factor κ-B pathway, which may contribute to the adaptive response of tissues to the stress of ischemia. Furthermore, both wine and vodka decreased multiple proinflammatory cytokines. This study provides a mechanism by which alcohol may be cardioprotective in ischemic myocardium.
Authors: Ivy A Ku; Ramin Farzaneh-Far; Eric Vittinghoff; Mary H Zhang; Beeya Na; Mary A Whooley Journal: Atherosclerosis Date: 2010-12-02 Impact factor: 5.162
Authors: Antonio D Lassaletta; Louis M Chu; Nassrene Y Elmadhun; Michael P Robich; Zachary G Hoffman; David J Kim; Frank W Sellke Journal: Eur J Cardiothorac Surg Date: 2012-09-18 Impact factor: 4.191
Authors: Louis M Chu; Antonio D Lassaletta; Michael P Robich; Yuhong Liu; Thomas Burgess; Roger J Laham; Joseph D Sweeney; Tun-Li Shen; Frank W Sellke Journal: Circulation Date: 2012-09-11 Impact factor: 29.690
Authors: Nassrene Y Elmadhun; Ahmed A Sadek; Ashraf A Sabe; Antonio D Lassaletta; Frank W Sellke Journal: Ann Thorac Surg Date: 2015-08-01 Impact factor: 4.330
Authors: Ulrich Hofmann; Susanne Knorr; Benjamin Vogel; Johannes Weirather; Anna Frey; Georg Ertl; Stefan Frantz Journal: Circ Heart Fail Date: 2014-06-26 Impact factor: 8.790
Authors: Elena Dozio; Alexis Elias Malavazos; Elena Vianello; Silvia Briganti; Giada Dogliotti; Francesco Bandera; Francesca Giacomazzi; Serenella Castelvecchio; Lorenzo Menicanti; Alexander Sigrüener; Gerd Schmitz; Massimiliano Marco Corsi Romanelli Journal: PLoS One Date: 2014-03-06 Impact factor: 3.240