Vitaly O. Kheyfets, Sushil Kumar, Paul M. Heerdt, Kenzo Ichimura, R. Dale Brown, Melissa Lucero, Ilham Essafri, Sarah Williams, Kurt R. Stenmark, Edda Spiekerkoetter
University of Colorado. Yale School of Medicine. Stanford University. he University of Queensland.
United States and Australia
International Journal of Molecular Sciences
Int J Mol Sci 2023; 24:
DOI: 10.3390/ijms24119746
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.
Category
Class IV. Pulmonary Hypertension Associated with Thromboembolic Disease
Animal Models of Pulmonary Vascular Disease and Therapy
Right Heart Dysfunction Associated with Pulmonary Vascular Disease
Genetic Factors Associated with Pulmonary Vascular Disease
Age Focus: No Age-Related Focus
Fresh or Filed Publication: Filed (PHiled). Greater than 1-2 years since publication
Article Access
Free PDF File or Full Text Article Available Through PubMed or DOI: Yes