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• W3131291258 startingPage "419" @default.
• W3131291258 abstract "Healthy aging drives structural and functional changes in the heart including maladaptive electrical remodeling, fibrosis and inflammation, which lower the threshold for cardiovascular diseases such as heart failure (HF) and atrial fibrillation (AF). Despite mixed results in clinical trials, Relaxin-therapy for 2-days reduced mortality by 37% at 180-days post-treatment, in patients with acute decompensated HF. Relaxin's short lifespan (2-3h) but long-lasting protective actions suggested that relaxin acts at a genomic level to reverse maladaptive remodeling in AF, HF and aging. Our recent studies showed that a 2-week treatment with Relaxin (0.4mg/kg/day) of aged (24months old F-344 rats) increases the expression of voltage-gated Na+ channels (mRNA, Nav1.5 and INa), connexin-43, abrogates inflammatory and immune responses and reverses myocardial fibrosis and cellular hypertrophy of the aged hearts. Relaxin acts directly at a wide range of cell types in the cardiovascular system that express its cognate GPCR receptor, RXFP1. RNA-seq analysis of young and aged hearts with and without Relaxin treatment revealed that normal aging altered the expression of ~10% of genes expressed in the ventricles, including: ion channels, components of fibrosis, hemodynamic biomarkers, immune and inflammatory responses which were reversed by Relaxin. The extensive cardiovascular remodeling caused by Relaxin was mediated through the activation of the Wnt/β-catenin signaling pathway which was otherwise suppressed by in adult cardiomyocytes intracellular by cytosolic Dickkopf1 (Dkk1). Wnt/β-catenin signaling is a mechanism that can explain the pleiotropic actions of Relaxin and the marked reversal of genomic changes that occur in aged hearts." @default.
• W3131291258 created "2021-03-01" @default.
• W3131291258 creator A5020551704 @default.
• W3131291258 creator A5025283915 @default.
• W3131291258 date "2021-01-01" @default.
• W3131291258 modified "2023-09-27" @default.
• W3131291258 title "Relaxin abrogates genomic remodeling of the aged heart" @default.
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