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- Title
Characterizing the Spatiotemporal Transcriptomic Response of the Right Ventricle to Acute Pressure Overload.
- Authors
Kheyfets, Vitaly O.; Kumar, Sushil; Heerdt, Paul M.; Ichimura, Kenzo; Brown, R. Dale; Lucero, Melissa; Essafri, Ilham; Williams, Sarah; Stenmark, Kurt R.; Spiekerkoetter, Edda
- 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.
- Subjects
TRANSCRIPTOMES; STRAINS &; stresses (Mechanics); PRINCIPAL components analysis; GENE expression; PULMONARY hypertension
- Publication
International Journal of Molecular Sciences, 2023, Vol 24, Issue 11, p9746
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms24119746