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

• Published in: Aging cell Vol. 18; no. 2; pp. e12894 - n/a
• Main Authors: Chacar, Stéphanie, Hajal, Joelle, Saliba, Youakim, Bois, Patrick, Louka, Nicolas, Maroun, Richard G., Faivre, Jean‐François, Fares, Nassim
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.04.2019; Wiley Open Access; John Wiley and Sons Inc
• Subjects: Administration, Oral; Age; Aging; Analysis; Animals; Antioxidants; Apoptosis; Apoptosis - drug effects; Ca2+/calmodulin-dependent protein kinase II; Calcineurin; Calcium-binding protein; Calmodulin; cardiac remodeling; Cardiology and cardiovascular system; Cardiomyocytes; Diet; DNA damage; Dose-Response Relationship, Drug; Echocardiography; Enzymes; Extracellular matrix; Extracellular signal-regulated kinase; Fibrosis; Glycogen; Glycogen synthase kinase 3; Heart; Heart enlargement; Human health and pathology; Hypertrophy; Inflammation; Kinases; Life Sciences; Male; Models, Biological; NF-AT protein; Original; Oxidative Stress; Oxidative Stress - drug effects; Phenolic compounds; Phenols; Phenols - administration & dosage; Phenols - pharmacology; Preservation; Rats; Rats, Wistar; Reactive Oxygen Species; Reactive Oxygen Species - metabolism; Ribonucleic acid; RNA; Senescence; Smad protein; Synthesis; T cells; Transcription factors; Transforming growth factors; Ventricle; Ventricular Dysfunction, Left; Ventricular Dysfunction, Left - metabolism; Ventricular Dysfunction, Left - prevention & control; Ventricular Remodeling; Ventricular Remodeling - drug effects; phenolic compounds; fibrosis; aging; hypertrophy; oxidative stress; cardiac remodeling
• ISSN: 1474-9718; 1474-9726; 1474-9726; 1474-9728
• DOI: 10.1111/acel.12894

With 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.