3f35a9d4b608d68c0b224a5f6205b8c6 pmc_35008601.pdf 57c43693329f9f7ab862a13bd2f7c60cc367abc7 pmc_35008601.pdf a33cdfb900983c831c0266182bc7c14f9228fe986a65accb821334aaf5e3cca5 pmc_35008601.pdf Title: Aging Impairs Reverse Remodeling and Recovery of Ventricular Function after Isoproterenol-Induced Cardiomyopathy Subject: Information about heart failure with reduced ejection fraction (HFrEF) in women and the potential effects of aging in the female heart is scarce. We investigated the vulnerability to develop HFrEF in female elderly mice compared to young animals, as well as potential differences in reverse remodeling. First, HF was induced by isoproterenol infusion (30 mg/kg/day, 28 days) in young (10-week-old) and elderly (22-month-old) female mice. In a second set of animals, mice underwent isoproterenol infusion followed by no treatment during 28 additional days. Cardiac remodeling was assessed by echocardiography, histology and gene expression of collagen-I and collagen-III. Following isoproterenol infusion, elderly mice developed similar HFrEF features compared to young animals, except for greater cell hypertrophy and tissue fibrosis. After beta-adrenergic withdrawal, young female mice experienced complete reversal of the HFrEF phenotype. Conversely, reversed remodeling was impaired in elderly animals, with no significant recovery of LV ejection fraction, cardiomyocyte hypertrophy and collagen deposition. In conclusion, chronic isoproterenol infusion is a valid HF model for elderly and young female mice and induces a similar HF phenotype in both. Elderly animals, unlike young, show impaired reverse remodeling, with persistent tissue fibrosis and cardiac dysfunction even after beta-adrenergic withdrawal. Keywords: heart failure; HFrEF; ageing; cardiac remodeling; ventricular dysfunction; reverseremodeling; female animals Author: Laia Yáñez-Bisbe, Anna Garcia-Elias, Marta Tajes, Isaac Almendros, Antonio Rodríguez-Sinovas, Javier Inserte, Marisol Ruiz-Meana, Ramón Farré, Núria Farré and Begoña Benito Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Fri Dec 24 10:33:54 2021 CET ModDate: Fri Dec 24 10:52:15 2021 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 12 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 2348658 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- KORLVE+VnURWPalladioL Type 1 Custom yes yes no 10 0 YQLDKR+URWPalladioL-Bold Type 1 Custom yes yes no 15 0 WDOQRT+URWPalladioL-Roma Type 1 Custom yes yes no 20 0 OENDXW+URWPalladioL-Ital Type 1 Custom yes yes no 24 0 UWJUYN+CMSY10 Type 1 Builtin yes yes no 28 0 DGBDNV+VnURWPalladioL-Bold Type 1 Custom yes yes no 32 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 40 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 44 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 48 0 IRWHZX+TimesNewRomanPSMT Type 1C WinAnsi yes yes no 60 0 CKUPDE+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 63 0 CAMXTK+EURM10 Type 1 Builtin yes yes no 88 0 MKBHEM+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 95 0 MKBHEN+PalatinoLinotype CID TrueType Identity-H yes yes yes 98 0 MKBHEO+PalatinoLinotype TrueType WinAnsi yes yes no 104 0 MKBHGA+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 107 0 MKBHEM+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 117 0 MKBHEO+PalatinoLinotype TrueType WinAnsi yes yes no 120 0 MKBHGA+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 123 0 MKBHEM+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 134 0 MKBHEO+PalatinoLinotype TrueType WinAnsi yes yes no 137 0 MKBHGA+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 140 0 MKBHEM+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 150 0 MKBHEO+PalatinoLinotype TrueType WinAnsi yes yes no 153 0 MKBHGA+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 156 0 MPUDFL+PazoMath Type 1 Builtin yes yes no 172 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-05-27 02:51:56 CEST RepresentationInformation: pmc_35008601.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2023-03-31 12:08:15 CEST Size: 2348658 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 353 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@44c8afef Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Children: Item: Title: Isoproterenol Infusion Induces HF with Subtle Particularities in Elderly Female Mice Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: Reverse Remodeling Is Distinctly Different in Young and Elderly Female Mice Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Materials and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Children: Item: Title: Animals Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Study Design Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Echocardiography Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: Histology Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Real-Time PCR Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: Statistical Analyses Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Info: Title: Aging Impairs Reverse Remodeling and Recovery of Ventricular Function after Isoproterenol-Induced Cardiomyopathy Author: Laia Yáñez-Bisbe, Anna Garcia-Elias, Marta Tajes, Isaac Almendros, Antonio Rodríguez-Sinovas, Javier Inserte, Marisol Ruiz-Meana, Ramón Farré, Núria Farré and Begoña Benito Subject: Information about heart failure with reduced ejection fraction (HFrEF) in women and the potential effects of aging in the female heart is scarce. We investigated the vulnerability to develop HFrEF in female elderly mice compared to young animals, as well as potential differences in reverse remodeling. First, HF was induced by isoproterenol infusion (30 mg/kg/day, 28 days) in young (10-week-old) and elderly (22-month-old) female mice. In a second set of animals, mice underwent isoproterenol infusion followed by no treatment during 28 additional days. Cardiac remodeling was assessed by echocardiography, histology and gene expression of collagen-I and collagen-III. Following isoproterenol infusion, elderly mice developed similar HFrEF features compared to young animals, except for greater cell hypertrophy and tissue fibrosis. After beta-adrenergic withdrawal, young female mice experienced complete reversal of the HFrEF phenotype. Conversely, reversed remodeling was impaired in elderly animals, with no significant recovery of LV ejection fraction, cardiomyocyte hypertrophy and collagen deposition. In conclusion, chronic isoproterenol infusion is a valid HF model for elderly and young female mice and induces a similar HF phenotype in both. Elderly animals, unlike young, show impaired reverse remodeling, with persistent tissue fibrosis and cardiac dysfunction even after beta-adrenergic withdrawal. 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