Intake of fermented beverages protect against acute myocardial injury: target organ cardiac effects and vasculoprotective effects
- 450 Downloads
Mild-to-moderate alcohol consumption has been associated with reduced risk of morbi/mortality from coronary artery disease. However, whether beer intake affords cardioprotection remains unclear. We investigated whether beer intake (alcohol-containing and alcohol-free brew) provides cardioprotection in a pig model of myocardial infarction (MI). Pigs were randomly assigned to: (1) be fed for 10 days a high-cholesterol diet (HC); (2) HC + low-dose beer (LB; 12.5 g alcohol/day); (3) HC + moderate-dose beer (MB; 25 g alcohol/day); or IV) HC + alcohol-free-MB (0.0 g alcohol/day) before MI induction and kept 21 days with the same regime. Scar size, echocardiography, biochemical and oxidative parameters were assessed. Myocardial tissue was obtained for molecular analysis and histology. All beer-fed animals were less prone to arrhythmogenesis during ischemia. At sacrifice, beer intake was associated with lower oxidative stress and higher HDL-antioxidant capacity. Within the ischemic myocardium beer-fed animals showed higher Akt/eNOS and AMPK activation and reduced sirtuin1-related apoptosis. Compared to controls beer intake was associated with lower lipid infiltration, higher TGFβ-related collagen fibril formation and diminished MMP9 activity in the fibrous tissue limiting scar size (HC + LB and HC + MB P < 0.05 and HC + alcohol-free-MB P = 0.068 vs. HC). Systolic-related parameters were similarly worsen post-MI in all groups and further deteriorated in control animals (P ≤ 0.05 vs. post-MI). At sacrifice, all animals showed a worsening in diastolic-related parameters but overall cardiac performance was improved in beer-fed animals regardless of the dose or alcohol content (P ≤ 0.05). In conclusion, beer intake reduces oxidative stress and apoptosis, activates RISK components and favors reparative fibrosis improving global cardiac performance.
KeywordsLarge animal model Beer intake Acute myocardial infarction Left ventricular remodeling Cardiac function
M. A. Canovas, P. Catalina, J. J Andres, and S. Florit support with animal handling and care and for the proper conduct of the experimental work is gratefully and highly recognized. The authors gratefully thank F. J. Rodriguez and M. A. Velasco for their technical assistance. This project is part of the PROMISE European Training Program (DE and SP). This work was supported by SAF 2010-16549 (to LB) from the Spanish Ministry of Science; CICS (to LB and GV); CIBEROBN06 (to LB); and Lilly Foundation (to LB). We thank Fundacion Jesus Serra-FIC, Barcelona, for their continuous support. GV is a recipient of a contract from the Innovation and Science Spanish Ministry (RyC-2009-5495).
Conflict of interest
The authors have no conflict of interest and no relation with industry.
- 3.Cal R, Castellano J, Revuelta-Lopez E, Aledo R, Barriga M, Farre J, Vilahur G, Nasarre L, Hove-Madsen L, Badimon L, Llorente-Cortes V (2012) Low-density lipoprotein receptor-related protein 1 mediates hypoxia-induced very low density lipoprotein-cholesteryl ester uptake and accumulation in cardiomyocytes. Cardiovasc Res 94:469–479. doi: 10.1093/cvr/cvs136 PubMedCrossRefGoogle Scholar
- 4.Callemien D, Jerkovic V, Rozenberg R, Collin S (2005) Hop as an interesting source of resveratrol for brewers: optimization of the extraction and quantitative study by liquid chromatography/atmospheric pressure chemical ionization tandem mass spectrometry. J Agric Food Chem 53:424–429. doi: 10.1021/jf040179n PubMedCrossRefGoogle Scholar
- 5.Castellano J, Aledo R, Sendra J, Costales P, Juan-Babot O, Badimon L, Llorente-Cortes V (2011) Hypoxia stimulates low-density lipoprotein receptor-related protein-1 expression through hypoxia-inducible factor-1alpha in human vascular smooth muscle cells. Arterioscler Thromb Vasc Biol 31:1411–1420. doi: 10.1161/ATVBAHA.111.225490 PubMedCrossRefGoogle Scholar
- 12.Gomez L, Paillard M, Price M, Chen Q, Teixeira G, Spiegel S, Lesnefsky EJ (2011) A novel role for mitochondrial sphingosine-1-phosphate produced by sphingosine kinase-2 in PTP-mediated cell survival during cardioprotection. Basic Res Cardiol 106:1341–1353. doi: 10.1007/s00395-011-0223-7 PubMedCrossRefGoogle Scholar
- 14.Hausenloy DJ, Baxter G, Bell R, Botker HE, Davidson SM, Downey J, Heusch G, Kitakaze M, Lecour S, Mentzer R, Mocanu MM, Ovize M, Schulz R, Shannon R, Walker M, Walkinshaw G, Yellon DM (2010) Translating novel strategies for cardioprotection: the Hatter Workshop Recommendations. Basic Res Cardiol 105:677–686. doi: 10.1007/s00395-010-0121-4 PubMedCrossRefGoogle Scholar
- 18.Ibanez B, Prat-Gonzalez S, Speidl WS, Vilahur G, Pinero A, Cimmino G, Garcia MJ, Fuster V, Sanz J, Badimon JJ (2007) Early metoprolol administration before coronary reperfusion results in increased myocardial salvage: analysis of ischemic myocardium at risk using cardiac magnetic resonance. Circulation 115:2909–2916. doi: 10.1161/CIRCULATIONAHA.106.679639 PubMedCrossRefGoogle Scholar
- 25.Krenz M, Baines CP, Yang XM, Heusch G, Cohen MV, Downey JM (2001) Acute ethanol exposure fails to elicit preconditioning-like protection in in situ rabbit hearts because of its continued presence during ischemia. J Am Coll Cardiol 37:601–607. doi: 10.1016/S0735-1097(00)01125-6 PubMedCrossRefGoogle Scholar
- 27.Levantesi G, Marfisi R, Mozaffarian D, Franzosi MG, Maggioni A, Nicolosi GL, Schweiger C, Silletta M, Tavazzi L, Tognoni G, Marchioli R (2011) Wine consumption and risk of cardiovascular events after myocardial infarction: results from the GISSI-Prevenzione trial. Int J Cardiol. doi: 10.1016/j.ijcard.2011.06.053 PubMedGoogle Scholar
- 37.Robich MP, Osipov RM, Nezafat R, Feng J, Clements RT, Bianchi C, Boodhwani M, Coady MA, Laham RJ, Sellke FW (2010) Resveratrol improves myocardial perfusion in a swine model of hypercholesterolemia and chronic myocardial ischemia. Circulation 122:S142–S149. doi: 10.1161/CIRCULATIONAHA.109.920132 PubMedCrossRefGoogle Scholar
- 40.Sattler KJ, Elbasan S, Keul P, Elter-Schulz M, Bode C, Graler MH, Brocker-Preuss M, Budde T, Erbel R, Heusch G, Levkau B (2010) Sphingosine 1-phosphate levels in plasma and HDL are altered in coronary artery disease. Basic Res Cardiol 105:821–832. doi: 10.1007/s00395-010-0112-5 PubMedCrossRefGoogle Scholar
- 41.Schwartz Longacre L, Kloner RA, Arai AE, Baines CP, Bolli R, Braunwald E, Downey J, Gibbons RJ, Gottlieb RA, Heusch G, Jennings RB, Lefer DJ, Mentzer RM, Murphy E, Ovize M, Ping P, Przyklenk K, Sack MN, Vander Heide RS, Vinten-Johansen J, Yellon DM (2011) New horizons in cardioprotection: recommendations from the 2010 National Heart, Lung, and Blood Institute Workshop. Circulation 124:1172–1179. doi: 10.1161/CIRCULATIONAHA.111.032698 PubMedCrossRefGoogle Scholar
- 46.Tang XL, Takano H, Xuan YT, Sato H, Kodani E, Dawn B, Zhu Y, Shirk G, Wu WJ, Bolli R (2005) Hypercholesterolemia abrogates late preconditioning via a tetrahydrobiopterin-dependent mechanism in conscious rabbits. Circulation 112:2149–2156. doi: 10.1161/CIRCULATIONAHA.105.566190 PubMedCrossRefGoogle Scholar
- 47.Theilmeier G, Schmidt C, Herrmann J, Keul P, Schafers M, Herrgott I, Mersmann J, Larmann J, Hermann S, Stypmann J, Schober O, Hildebrand R, Schulz R, Heusch G, Haude M, von Wnuck-Lipinski K, Herzog C, Schmitz M, Erbel R, Chun J, Levkau B (2006) High-density lipoproteins and their constituent, sphingosine-1-phosphate, directly protect the heart against ischemia/reperfusion injury in vivo via the S1P3 lysophospholipid receptor. Circulation 114:1403–1409. doi: 10.1161/CIRCULATIONAHA.105.607135 PubMedCrossRefGoogle Scholar
- 48.Thomas WP, Gaber CE, Jacobs GJ, Kaplan PM, Lombard CW, Moise NS, Moses BL (1993) Recommendations for standards in transthoracic two-dimensional echocardiography in the dog and cat. Echocardiography Committee of the Specialty of Cardiology, American College of Veterinary Internal Medicine. J Vet Intern Med 7:247–252. doi: 10.1111/j.1939-1676.1993.tb01015.x PubMedCrossRefGoogle Scholar
- 49.Vaziri ND, Moradi H, Pahl MV, Fogelman AM, Navab M (2009) In vitro stimulation of HDL anti-inflammatory activity and inhibition of LDL pro-inflammatory activity in the plasma of patients with end-stage renal disease by an apoA-1 mimetic peptide. Kidney Int 76:437–444. doi: 10.1038/ki.2009.177 PubMedCrossRefGoogle Scholar
- 52.Vilahur G, Hernandez-Vera R, Molins B, Casani L, Duran X, Padro T, Badimon L (2009) Short-term myocardial ischemia induces cardiac modified C-reactive protein expression and proinflammatory gene (cyclo-oxygenase-2, monocyte chemoattractant protein-1, and tissue factor) upregulation in peripheral blood mononuclear cells. J Thromb Haemost 7:485–493. doi: 10.1111/j.1538-7836.2008.03244.x PubMedCrossRefGoogle Scholar