Characterizing the Spatiotemporal Transcriptomic Response of the Right Ventricle to Acute Pressure Overload
Year: 2023
Type: article
Abstract: This study analyzed microarray data of right ventricular (RV) tissue from rats exposed to pulmonary embolism to understand the initial dynamic transcriptional response to mechanical stress and compare it with experimental pulmonary hypertension (PH) models. The dataset included samples harvested from 55 rats at 11 different time points or RV locations. We performed principal component analysis (PCA) to explore clusters based on spatiotemporal gene expression. Relevant pathways were identified from fast gene set enrichment analysis using PCA coefficients. The RV transcriptomic signature was measured over several time points, ranging from hours to weeks after an acute increase in mechanical stress, and was found to be highly dependent on the severity of the initial insult. Pathways enriched in the RV outflow tracts of rats at 6 weeks after severe PE share many commonalities with experimental PH models, but the transcriptomic signature at the RV apex resembles control tissue. The severity of the initial pressure overload determines the trajectory of the transcriptomic response independent of the final afterload, but this depends on the location where the tissue is biopsied. Chronic RV pressure overload due to PH appears to progress toward similar transcriptomic endpoints.
DOI: 10.3390/ijms24119746
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,780
Awards: Inter-ventricular decoupling is an overlooked contributor to right ventricular myocardial stress and dysfunction in pediatric pulmonary hypertension, G331086912, G40905347, Complement Mediated Remodeling in Pulmonary Vascular Disease, Characterizing and Improving the Microvascular-Cardiomyocyte Interphase in Pressure-Overloaded Right Heart Failure, Cause and effect of transient changes in stress, gene expression, and RV fiber orientation during RV remodeling, and its impact on RV function and inter-ventricular coupling in pulmonary hypertension, G7819143234, Translational Pulmonary Vascular Biology Program, Yale Clinical and Translational Science Award, What triggers RV Fiber Re-Orientation in response to RV pressure overload, and what is its Consequence on Inter-Ventricular Decoupling?
OpenAlex ID: W4379468349