Transcriptome-wide analysis associates ID2 expression with combined pre- and post-capillary pulmonary hypertension

Heart failure with preserved ejection fraction (HFpEF) patients who develop pulmonary hypertension (PH) have an increased risk of death, with combined pre- and post-capillary PH (CpcPH) having the highest risk. However, the mechanism behind PH development in HFpEF is poorly understood. We aimed to i...

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Bibliographic Details
Published in:Scientific reports 2019-12, Vol.9 (1), p.19572-10, Article 19572
Main Authors: Arwood, Meghan J, Vahabi, Nasim, Lteif, Christelle, Sharma, Ravindra K, Machado, Roberto F, Duarte, Julio D
Format: Article
Language:English
Subjects:
Animals
Cardiac Catheterization
Congestive heart failure
Female
Gene expression
Heart failure
Heart Failure - genetics
Heart Failure - therapy
Humans
Hypertension
Hypertension, Pulmonary - genetics
Hypertension, Pulmonary - therapy
Inhibitor of Differentiation Protein 2 - genetics
Male
Mice
Middle Aged
Mitochondria
Peripheral Blood Stem Cells - metabolism
Polymerase Chain Reaction
Pulmonary hypertension
Ribonucleic acid
RNA
Transcriptome - genetics
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Summary:Heart failure with preserved ejection fraction (HFpEF) patients who develop pulmonary hypertension (PH) have an increased risk of death, with combined pre- and post-capillary PH (CpcPH) having the highest risk. However, the mechanism behind PH development in HFpEF is poorly understood. We aimed to identify transcriptomic associations with PH development in HFpEF. Blood was collected from 30 HFpEF patients: 10 without PH, 10 with isolated post-capillary PH, and 10 with CpcPH. Gene expression measurements were completed using transcriptome-wide RNA sequencing. Gene expression differences were compared using a quasi-likelihood method adjusting for age, sex, race, and smoking-status. Biological pathways were compared using global gene expression differences. A replication in 34 additional heart failure patients and a validation in lung tissue from a representative mouse model were completed using quantitative PCR. Six differentially expressed genes were identified when comparing transcriptomics between subjects with CpcPH and those without PH. When tested in additional subjects, only the association with ID2 replicated. Consistent with clinical findings, Id2 expression was also upregulated in mice with HFpEF and PH. Pathway analysis identified proliferative and mitochondrial pathways associated with CpcPH. Thus, these patients may possess systemic pathophysiological differences similar to those observed in pulmonary arterial hypertension patients.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-019-55700-y