Long-term intake of phenolic compounds attenuates age-related cardiac remodeling

International audienceWith the onset of advanced age, cardiac-associated pathologies have increased in prevalence. The hallmarks of cardiac aging include cardiomyocyte senescence, fibroblast proliferation, inflammation, and hypertrophy. The imbalance between levels of reactive oxygen species (ROS) and antioxidant enzymes is greatly enhanced in aging cells, promoting cardiac remodeling. In this work, we studied the long-term impact of phenolic compounds (PC) on age-associated cardiac remodeling. Three-month-old Wistar rats were treated for 14 months till middle-age with either 2.5, 5, 10, or 20 mg kg-1 day-1 of PC. PC treatment showed a dose-dependent preservation of cardiac ejection fraction and fractional shortening as well as decreased hypertrophy reflected by left ventricular chamber diameter and posterior wall thickness as compared to untreated middle-aged control animals. Analyses of proteins from cardiac tissue showed that PC attenuated several hypertrophic pathways including calcineurin/nuclear factor of activated T cells (NFATc3), calcium/calmodulin-dependent kinase II (CAMKII), extracellular regulated kinase 1/2 (ERK1/2), and glycogen synthase kinase 3ß (GSK 3ß). PC-treated groups exhibited reduced plasma inflammatory and fibrotic markers and revealed as well ameliorated extracellular matrix remodeling and interstitial inflammation by a downregulated p38 pathway. Myocardia from PC-treated middle-aged rats presented less fibrosis with suppression of profibrotic transforming growth factor-ß1 (TGF-ß1) Smad pathway. Additionally, reduction of apoptosis and oxidative damage in the PC-treated groups was reflected by elevated antioxidant enzymes and reduced RNA/DNA damage markers. Our findings pinpoint that a daily consumption of phenolic compounds could preserve the heart from the detrimental effects of aging storm

Predictors of right ventricular function as measured by tricuspid annular plane systolic excursion in heart failure

<p>Abstract</p> <p>Introduction</p> <p>Tricuspid Annular Plane Systolic Excursion (TAPSE) has independent prognostic value in heart failure patients but may be influenced by left ventricular (LV) ejection fraction. The present study assessed the association of TAPSE and clinical factors, global and regional LV function in 634 patients admitted for symptomatic heart failure.</p> <p>Methods & Results</p> <p>TAPSE were correlated with global and regional measures of longitudinal LV function, segmental wall motion scores and measures of diastolic LV function as measured from transthoracic echocardiography.</p> <p>LV ejection fraction, wall motion index scores, atrio-ventricular annular plane systolic excursion of the mitral annulus were significantly related to TAPSE. Septal and posterior mitral annular plane systolic excursion (β = 0.56, p < 0.0001 and β = 0.35, p = 0.0002 per mm, respectively) and non-ischemic etiology of heart failure (β = 1.3, p = 0.002) were independent predictors of TAPSE, R²= 0.28, p < 0.0001. The prognostic importance of TAPSE was not dependent of heart failure etiology or any of the other clinical factors analyzed, p_interaction= NS.</p> <p>Conclusion</p> <p>TAPSE is reduced with left ventricular dysfunction in heart failure patients, in particular with reduced septal longitudinal motion. TAPSE is decreased in patients with heart failure of ischemic etiology. However, the absolute reduction in TAPSE is small and seems to be of minor importance in the clinical utilization of TAPSE whether applied as a measure of right ventricular systolic function or as a prognostic factor.</p

TRPC-like conductance mediates restoration of intracellular Ca2+ in cochlear outer hair cells in the guinea pig and rat

Ca2+ signalling is central to cochlear sensory hair cell physiology through its influence on sound transduction, membrane filter properties and neurotransmission. However, the mechanism for establishing Ca2+ homeostasis in these cells remains unresolved. Canonical transient receptor potential (TRPC) Ca2+ entry channels provide an important pathway for maintaining intracellular Ca2+ levels. TRPC3 subunit expression was detected in guinea pig and rat organ of Corti by RT-PCR, and localized to the sensory and neural poles of the inner and outer hair cells (OHCs) by confocal immunofluorescence imaging. A cation entry current with a TRPC-like phenotype was identified in guinea pig and rat OHCs by whole-cell voltage clamp. This slowly activating current was induced by the lowering of cytosolic Ca2+ levels ([Ca2+]i) following a period in nominally Ca2+-free solution. Activation was dependent upon the [Ca2+]o and was sustained until [Ca2+]i was restored. Ca2+ entry was confirmed by confocal fluorescence imaging, and rapidly recruited secondary charybdotoxin- and apamin-sensitive KCa currents. Dual activation by the G protein-coupled receptor (GPCR)–phospholipase C–diacylglycerol (DAG) second messenger pathway was confirmed using the analogue 1-oleoyl-2-acetyl-sn-glycerol (OAG). Ion substitution experiments showed that the putative TRPC Ca2+ entry current was selective for Na+ > K+ with a ratio of 1: 0.6. The Ca2+ entry current was inhibited by the TRPC channel blocker 2-aminoethyl diphenylborate (2APB) and the tyrosine kinase inhibitor, erbstatin analogue. We conclude that TRPC Ca2+ entry channels, most likely incorporating TRPC3 subunits, support cochlear hair cell Ca2+ homeostasis and GPCR signalling