Abstract
Abstract P3052: RNA Binding Protein Csdc2 Is Required For Metabolic And Cardiac Stress Responses
Circulation research, Vol.133(Suppl_1)
08/04/2023
DOI: 10.1161/res.133.suppl_1.P3052
Abstract
Abstract only Post transcriptional gene regulation (PTGR) mediated by networks of microRNAs and RNA binding proteins (RBP's) controls mRNA processing, localization, and expression. Hundreds of microRNAs and RBPs are expressed in heart, and much remains unknown regarding PTGR’s influence on cardiovascular health and disease. Through bioinformatic analyses, we identified Csdc2 as a cardiac-enriched RBP that is consistently downregulated in failing hearts. Csdc2’s paralog, Carshp1, controls metabolic gene expression in liver through PPARα. We hypothesize that Csdc2 plays key roles in cardio-metabolic stress. To address this, we first assessed mRNA-seq changes in neonatal rat cardiomyocytes after overexpression and knockdown of Csdc2. Pathway analyses revealed reciprocal dysregulation of fatty acid metabolism, ion channels, and cytoskeletal and sarcomere genes. We generated constitutive Csdc2-KO mice, which are viable with no overt baseline phenotypes. Cardiac phenotyping revealed that Csdc2-KO mice have slightly decreased PR interval (~10%, p=1.3e-4, n=16-22) but maintain normal cardiac structure/function. To assess Csdc2’s potential role in metabolic stress, mice were fed a high-fat-diet for 10 weeks and monitored for lean/fat mass and insulin/glucose tolerances. Csdc2-KO mice gained 20% more weight than wildtype littermates (p=0.04, n=13-18) and developed insulin resistance (p<0.01). To test if Csdc2 loss influences cardiac stress, normal chow cohorts were subjected to microsurgery-induced myocardial infarction (MI); Csdc2-KO mice showed ~2-fold increase in mortality within two weeks (70% versus 40% for wildtype). Echocardiographic measures support that Csdc2-KO hearts have larger infarcts, dilation without compensatory remodeling and worse systolic function. Together, these data highlight Csdc2 as a disease-relevant RBP that controls cardio-metabolic stress responses.
Details
- Title: Subtitle
- Abstract P3052: RNA Binding Protein Csdc2 Is Required For Metabolic And Cardiac Stress Responses
- Creators
- Jared M McLendon - University of IowaXiaoming Zhang - University of IowaRyan L Boudreau - University of Iowa
- Resource Type
- Abstract
- Publication Details
- Circulation research, Vol.133(Suppl_1)
- DOI
- 10.1161/res.133.suppl_1.P3052
- ISSN
- 0009-7330
- eISSN
- 1524-4571
- Language
- English
- Date published
- 08/04/2023
- Academic Unit
- Fraternal Order of Eagles Diabetes Research Center; Iowa Neuroscience Institute; Internal Medicine; Cardiovascular Medicine
- Record Identifier
- 9984479659602771
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