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

Abstract

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.

The Histone Deacetylase Inhibitor Suberoylanilide Hydroxamic Acid (SAHA) Restores Cardiomyocyte Contractility in a Rat Model of Early Diabetes

“…Although other mechanisms cannot be excluded, these findings support the hypothesis that the positive effects induced by low-dose SAHA treatment on cardiomyocyte performance can be attributed, at least in part, to its capacity of reducing ROS accumulation, an early event in the diabetic heart following diabetes-induced metabolic changes. This interpretation is also supported by previous reports showing that scavenging of ROS improves calcium homeostasis and attenuates cardiac derangement in multiple models of heart disease, including heart failure, hypertrophy, diabetic cardiomyopathy, and aging [16,32,33]. The difference in metabolic activity between control and diabetic rats, revealed through MTS assay, could be related to an impairment of mitochondrial function induced by the oxidative stress, in particular the loss of mtDNA integrity that can have consequences on bioenergetics and metabolism [34].…”

Plant Phenolics: Bioavailability as a Key Determinant of Their Potential Health-Promoting Applications

“…For instance, it was observed that characteristics of metabolic syndrome induced with a high-fat, high-fructose diet in Wistar rats were attenuated by supplementation with a grape pomace that was rich in 26 different phenolic compounds [ 82 ]. Additionally, Wistar rats fed for 14 months with an extract rich in malvidin, delphinidin, rutin, quercetin, catechin, coumaric acid, kaempferol and trans-cinnamic acid prevented hypertrophy, inflammation, fibrosis and cardiomyocytes apoptosis [ 83 ]. Finally, vasorelaxant activity of a ferulic acid metabolite, ferulic acid-4- O -sulfate, was also demonstrated in both isolated mouse arteries and anesthetized mice [ 84 ].…”

Potential health benefits of phenolic compounds in grape processing by-products

“…The long-term cardioprotective effect of a polyphenolrich mixture of Cabernet Sauvignon, Marselan, and Syrah varieties was also confirmed using middle-aged Wistar rats (Chacar et al, 2019). Among the polyphenols identified in the extract were malvidin, delphinidin, rutin, quercetin, catechin, coumaric acid, kaempferol, and trans-cinnamic acid, which could explain the prevention of hypertrophy, inflammation, fibrosis, and cardiomyocyte apoptosis observed upon administration of the extract (Chacar et al, 2018;.…”