Transcriptional changes in right ventricular tissues are enriched in the outflow tract compared with the apex during chronic pulmonary embolism in rats.
Moderate to severe pulmonary embolism (PE) can cause pulmonary arterial hypertension and right ventricular (RV) heart damage. Previous studies from our laboratory indicate that the basal outflow tract of the RV is injured and has acute inflammation followed by tissue remodeling while the apex appears normal. The present studies examine transcription responses to chronic PE in RV apex and outflow tracts using DNA microarrays to identify transcription responses by region. Changes predominated in the RV outflow tract (8,575 genes showed >/=1.5-fold expression change). Gene ontology and KEGG analyses indicated a significant decrease in genes involved in cellular respiration and energy metabolism and increases in inflammatory cell adhesion molecules and extracellular matrix proteins. Signal pathways for wound healing such as fibroblast growth factor, collagen synthesis, and CCN proteins (named for the first three members of the family: cysteine-rich protein 61, connective tissue growth factor, and nephroblastoma overexpressed gene) were strongly upregulated. In comparison, few genes (422) showed significant change in the RV apex tissue. Apex-selective genes included two genes affecting metabolism and a stretch-sensitive transcription factor (ankyrin repeat domain 1). We conclude that the RV outflow tract is subject to strong proinflammatory and profibrotic remodeling transcriptional responses in chronic PE. Severe loss of genes involved in cellular respiration is consistent with previous histology indicating a shift in cell types present within the outflow tract tissue away from highly energy-dependant cardiomyocytes to less metabolically active cells during remodeling. The apex region of the RV had few compensating adaptations.
Zagorski
John
J
Department of Emergency Medicine, James G. Cannon Research Center, Carolinas Medical Center, Charlotte, North Carolina 28203, USA.
Obraztsova
Maria
M
Gellar
Michael A
MA
Kline
Jeffrey A
JA
Watts
John A
JA
D000704:Analysis of Variance; D000818:Animals; D002908:Chronic Disease; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006352:Heart Ventricles / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D009206:Myocardium / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D011655:Pulmonary Embolism / Q000235:genetics* / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014158:Transcription, Genetic