Year: 2025
Type: article
Study design: Observational Study
Abstract: ABSTRACT The molecular mechanisms driving right ventricular (RV) adaptation to stress and failure in end‐stage heart failure (HF) are largely unknown. We aimed to characterize myocardial transcriptional changes in the RV caused by left sided HF and comparing RV compensation to failure. Additionally, we compared transcriptomic changes between right and left ventricular (LV) failure. Paired right and left ventricular myocardial tissue samples were obtained from 33 human subjects with end stage HF referred for transplantation and 8 control donors with unused transplant hearts. RV samples from end stage HF subjects were subdivided into compensated ( n = 25) and failing ( n = 8) categories based on pulmonary artery pulsatility index of < 1.85. All samples underwent bulk tissue RNA‐sequencing. We compared gene expression between groups and performed pathway enrichment analysis. Pathways related to fatty acid metabolism and mitochondrial function were negatively enriched, while extracellular structure‐related pathways were positively enriched in stressed RVs (compensated and failing) compared to controls. Compensated and failing RVs were differentiated by transcriptional changes in protein production/processing and immune system pathways. PPAR signaling and fatty acid metabolism pathways were consistently enriched in the RV compared to the LV. The RV has a distinct transcriptional signature under stress and in failure. Overlapping molecular mechanisms may underlie RV failure in pulmonary arterial hypertension and HF. Fatty Acid metabolism and associated signaling pathways appear enriched in the RV compared to the LV.
Source: Pulmonary Circulation
DOI: 10.1002/pul2.70090
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,310
Funders: U.S. Department of Veterans Affairs, American Heart Association, Vanderbilt University, Georgia Clinical and Translational Science Alliance, National Institutes of Health, U.S. Food and Drug Administration, National Heart, Lung, and Blood Institute, National Eye Institute, National Cancer Institute, National Center for Research Resources
Awards: G1344704808, G1785014797, G2043477120, G2717209771, A novel molecular target in atrial fibrillation, G338527938, G3433274139, G442534625, G4552961446, G563474107, G5853943267, Clinical Outcomes for Genetic Subtypes of Early-onset Atrial Fibrillation Across Diverse Genetic Ancestries, The Vanderbilt Institute for Clinical and Translational Research (VICTR) UL1, Clinical, Genetic, and Proteomic Risk Factors for Pulmonary Hypertension in Heart Failure, G6839816254, G7220527126, VANTAGE:Consolidation to create the Vanderbilt Technologies for Advanced Genomics, A molecular phenotype of combined pulmonary hypertension, G8489868044, G9000060478, G9000081609, G9000127534, G9000236029, G9000300101, Clinical and Translational Training Program in Pulmonary Medicine, The MObile Health InterVEntion in Pulmonary Arterial Hypertension (MOVE PAH) Study, Cancer Center Support Grant, Clinical and Mechanistic Understanding of Right Ventricular Steatosis in Pulmonary Arterial Hypertension, MhOVE-PPH Study: Mobile health interventiOn to improVe Exercise in Pediatric PH
OpenAlex ID: W4409768485