Long-Term Impact of Western Diet on Right Ventricular Transcriptome: Uncovering Sex-Specific Patterns in C57BL/6J Mice
Year: 2025
Type: article
Abstract: The Western diet (WD) has been linked to various structural and functional alterations in the left ventricle (LV), but the molecular response of the right ventricle (RV) remains largely unknown. Given the RV's distinct anatomical and functional characteristics, it is crucial to understand how long-term WD exposure affects RV gene expression, especially in a sex-specific context. Our objective was to perform gene expression profiling of the RV late responses to WD in wild-type mice. Male and female C57BL/6J mice were fed a WD for 125 days from 300 to 425 days of age, and RV tissues were collected at 530 and 640/750 (female/male) days. mRNA sequencing was performed on RV tissues to identify differentially expressed genes (DEGs) between WD-fed and normal diet (ND)-fed groups. Data processing and analysis were conducted using the STAR aligner and DESeq2. WD-induced RV transcriptomic changes were characterized by differential expression of genes associated with cardiac remodeling and transcriptional regulation in both sexes. In females, additional genes showing altered expression were associated with immune response, whereas in males, changes were more limited, primarily involving genes related to circadian rhythm and cardiac remodeling. Echocardiography revealed modest, sex-specific differences: WD-fed females showed a decrease in right-ventricular internal diameter in diastole and a trend toward increased pulmonary trunk diameter, whereas males showed no notable changes. These exploratory results suggest that WD is associated with modest transcriptomic changes in the RV in both sexes, with only minor structural differences observed in females, indicating subtle sex-specific effects after a switch to normal chow.
DOI: 10.3390/ijms27010259
Authors: Ani Stepanyan, Siras Hakobyan, Agnieszka Brojakowska, Malik Bisserier, Roksana Zakharyan, Suren Davitavyan, Tamara Sirunyan, Gisane Khachatryan, Mary K. Khlgatian, Shihong Zhang, Ania Baghoomian, Susmita Sahoo, Lahouaria Hadri, Venkata Naga Srikanth Garikipati, Arsen Arakelyan, David A. Goukassian
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,499
Awards: WE ANTICIPATE THAT THE RESULTS OF OUR PROPOSED WORK MAY BE BENEFICIAL FOR HUMAN SPACE EXPLORATION AND COULD (1) DETERMINE SINGLE LOW-DOSE 1H 56FE AND MIXED FIELD DOSE-RESPONSES RADIO-BIOLOGICALLY EFFECTIVE IR THRESHOLDS IN THE HEART AND CARDIAC VASCULATURE AND WHETHER GENDER DIFFERENCES COULD MODIFY RADIO-BIOLOGICALLY EFFECTIVE IR THRESHOLDS FOR CV RISK ESTIMATES; 2) DETERMINE WHETHER SPACE RADIATION LEADS TO MODIFICATIONS IN THE CIRCULATING EXOSOMAL CARGO CONTENTS AND WHETHER IR-INDUCED EXOSOMAL CARGO MODULATIONS ARE REFLECTIVE OF SUBCLINICAL CHANGES IN THE CELLS AND ORGANS OF ORIGIN; 3) ASCERTAIN IF MODULATIONS OF EXOSOMAL CARGO MAY BE REPRESENTATIVE OF CHRONIC OXIDATIVE STRESS AND INFLAMMATION AND COULD SERVE AS EARLY BIOMARKERS OF IR-INDUCED CV DISEASE INITIATION AND PROGRESSION; 4) INTEGRATE PHYSIOLOGICAL CV ENDPOINT DATA SETS WITH GENE EXPRESSION AND EPIGENETIC DATA TO IDENTIFY BIO-MARKERS IN BIO-FLUIDS THAT COULD BE USED FOR PREDICTION OF ASYMPTOMATIC CV DISEASE IN THE SETTING OF SPACE IR WHICH WILL INCLUDE KNOWN EARLY AND INTERMEDIATE BIO-MARKERS OF CARDIAC DAMAGE INFLAMMATION AND OXIDATIVE STRESS AS WELL AS CURRENTLY UNKNOWN NOVEL RADIATION-ASSOCIATED CARDIAC BIO-MARKERS., Targeting Endothelial SIN3A Using Lung-Specific mRNA Therapy In Pulmonary Arterial Hypertension
OpenAlex ID: W7117326491