BEER AND THE HEART: INSIGHTS ON THE EFFECTS ON ALCOHOLIC AND NON-ALCOHOLIC BEER Lina Badimon Cardiovascular Research Center (CRC) CSIC-ICCC Barcelona 7 TH EUROPEAN BEER AND HEALTH SYMPOSIUM BRUSSELS -2014
Mortality causes: impact of CVD WORLD OMS 2010 CVDs LEADING CAUSE OF DEATH (30.5% total)
Recomended doses Alcohol effect on GLOBAL DEATH -30g/day men: 2-3 beers, 2-3 glasses of wine -20g/day women: 1-2 beers, 1-2 glass of wine Corrao et al 2000 - Two drinks per day men - One drink per day women One drink = 12 oz. ( 350 ml) of BEER 4 oz. ( 120ml) of WINE 1.5 oz. ( 45 ml) ofspirits Alcohol intake in young and pregnant = 0
Moderate fermented beverages intake.. Atheroprotective effects (lower incidence of CVD) Cardioprotective effects?
Certain pathological conditions (HYPERCHOLESTEROLEMIA) G. Vilahur, L. Casani, L.Badimon. Atherosclerosis 2012 CARDIAC REMODELING Repair process of the necrotic area promoting myocardial scarring G. Vilahur, O. Juan-Babot, L.Badimon. J Mol Cell Cardiol 2011 Aggravate and/or intensify cardiac structural remodeling adversely affecting cardiac function Beer intake affords cardiac protection and improves scar formation post- AMI in the setting of dyslipidemia???
Study protocol Beer intake affords cardiac protection during ischemia??? 10 days AMI 21 days hypercholesterolemic diet HC CONTROL 12.5g alcohol/day (LOW DOSE) 25g alcohol/day (MODERATE DOSE) 0g alcohol/day (ALCOHOL-FREE) Beer intake affords cardiac protection in the remodeling phase??? SYSTEMS BIOLOGY APPROACH FUNCTIONAL STUDIES CARDIAC FUNCTION CORONARY FUNCTION HISTOLOGICAL STUDIES INFARCT SIZE FIBROSIS / SCAR CARDIAC LIPIDS 0g alcohol/day (ALCOHOL-FREE) 25g alcohol/day (MODERATE DOSE) 12.5g alcohol/day (LOW DOSE) HC CONTROL MOLECULAR STUDIES RISK activation enos activity APOPTOSIS Systemic effects??? SACRIFICE TRANSCRIPTOMICS (ARRAYS)
Cardiac protection during ISCHEMIA?? % episodes VF / animal Incidence of ventricular fibrilations and mortality during STEMI-AMI 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 85,71% 22% Incidence of deaths Incidence of VF 28,57% 0% 0% 0% HC HC+LB HC+MB HC+alcohol-free MB 14,29% 71,43% 4,5 Number of VF/ animal 4 3,5 3 2,5 P<0.05 : AMELIORATES MYOCARDIAL ADAPTATION IN THE SETTING OF ACUTE MI 2 1,5 1,5 0 HC HC+LB HC+MB HC+alcohol-free-MB G. Vilahur, L. Casani, J.Guerra, L.Badimon. Basic Res Cardiol 2012
Cardiac protection post-ami: scar size Scar size /% AAR Coronary artery 50 45 40 35 30 25 20 15 10 5 0 Scar size P=0.07 p=0.068 HC HC+LB HC+MB HC+alcoholfree MB p<0.05 vs HC G. Vilahur, L. Casani, J.Guerra, L.Badimon. Basic Res Cardiol 2012
Scar size and left ventricle remodeling HC HC+LB HC+MB HC+alcoholfree MB 229 ± 11 g 227 ± 10 g 233 ± 9 g 222 ± 7 g :REDUCES SCAR SIZE WITHOUT MODIFYING LV ARCHITECTURE
Cardiac protection post-ami: molecular mechanisms Cardioprotective signaling pathways (RISK) Adenosine Bradykinin Opioids PIP2 PKA PIP3 PDK1 PI3K perk MTP P-eNOS NO GC cgmp PKG PKC Akt P-mdm2 SNO Caspase-3 perk PKC P70S6K p53 GSK BAD MTP APOPTOSIS MTP slow ph recovery
Active Caspase3/βactin Sirt1/18SrRNA Apoptosis execution : :ACTIVATES CARDIOPROTECTIVE KINASES AND REDUCES APOPTOSIS EXECUTION Ischemic Non-Ischemic 300 250 200 Active Caspasa-3 140 120 100 Sirtuin-1 (antioxidant) 150 100 50 80 60 40 20 0 HC HC+LB HC+MB HC+ alcoholfree MB 0 HC HC+LB HC+MB HC+alcoholfree MB p<0.05 vs HC
Apoptosis cell death INFARCT SIZE
WHICH ARE THE GENES INVOLVED IN THE REGULATION OF THE OBSERVED FUNCTIONAL BENEFITS IN THE HEART? TRANSCRIPTOMICS Ischemic border zone G. Vilahur, S. Camino, L. Badimon. Upublished data
Porcine Genome Array - Microarray expression analysis Ischemic border zone 35.000 genes Differential expressed Genes: Software Partek Genomics Suite Networks and functional analysis: Software Ingenuity Pathways Analysis G. Vilahur, S. Camino, L. Badimon. Upublished data
PCA analysis gene cluster HC LB MB G. Vilahur, S. Camino, L. Badimon. Upublished data
Associated Network Functions G. Vilahur, S. Camino, L. Badimon. Upublished data
Systemic vasculoprotective effects
Does been intake improves hypercholesterolemiarelated endothelial dysfunction? 10 days + 12.5g alcohol/day (LOW DOSE) 25g alcohol/day (MODERATE DOSE) 0g alcohol/day (ALCOHOL-FREE) HC CONTROL - CORONARY ENDOTHELIAL FUNCTION - CORONARY OXIDATIVE DNA-DAMAGE Akt/eNOS ACTIVATION G. Vilahur, L. Casani, G. Mendieta, RM. Lamuela-Raventos,R. Estruch, L. Badimon. In review
CORONARY FUNCTION - REACTIVITY Changes in coronary regional blood flow upon pharmacological induction Open-chest approach Fluoroscopy guidance (Rx) LAD Pressure Transducer LAD Myocardium Catheter Circumflex G. Vilahur, L. Casani, G. Mendieta, RM. Lamuela-Raventos,R. Estruch, L. Badimon. Under review
% vasodilation % vasodilation Changes in coronary regional blood flow upon pharmacological induction 120 100 80 60 40 Acetylcholine (M) 120 100 80 60 40 Calcium Ionophore (M) 20 20 0 1,0E-09 1,0E-08 1,0E-07 1,0E-06 0 1,0E-09 1,0E-08 1,0E-07 1,0E-06 120 100 SNP (M) 80 60 40 20 0 1,0E-07 1,0E-06 1,0E-05 G. Vilahur, L. Casani, G. Mendieta, RM. Lamuela-Raventos,R. Estruch, L. Badimon. Under review
CORONARY ARTERY: Akt/eNOS signaling P-Akt/Akt P-eNOS/eNOS 6 5 4 3 2 1 0 HC P-Akt/Akt HC+MD OH-free beer HC+LD Beer HC+MD Beer 3 2 1 0 HC P-eNOS/eNOS HC+MD OH-free beer HC+LD Beer HC+MD Beer P-Akt Akt P-eNOS enos G. Vilahur, L. Casani, G. Mendieta, RM. Lamuela-Raventos,R. Estruch, L. Badimon. Under review
CORONARY ARTERY: DNA-oxidative damage (8-OHdG staining) HC HC+OH-free beer HC+LD Beer HC+MD Beer 8-OHdG G. Vilahur, L. Casani, G. Mendieta, RM. Lamuela-Raventos,R. Estruch, L. Badimon. Under review
TAKE HOME MESSAGES Light-to-moderate regular beer intake (with and without alcohol) during 31 days exerts cardioprotection overcoming the detrimental effects associated with dyslipidemia in the ischemic myocardium Antioxidant properties of beer rather than alcohol in itself may protect against hyperlipemia-induced coronary endothelial dysfunction by favorably counteracting vascular oxidative damage and activating the Akt/eNOS pathway.
Lina Badimon Dra. Laura Casaní Dr. Oriol Juan-Babot Dr. José Mª Guerra (HSCSP) Mª. Angeles Cánovas Pablo Catalina Fco.J. Rodriguez Mª. Angeles Velasco