ID2 gene expression was significantly upregulated (fold-change 2.1) in peripheral blood mononuclear cells of heart failure patients with combined pre- and post-capillary pulmonary hypertension compared to those without pulmonary hypertension.
Observational (n=64)
No
Are specific transcriptomic profiles associated with the development of combined pre- and post-capillary pulmonary hypertension in patients with HFpEF?
ID2 expression is associated with combined pre- and post-capillary pulmonary hypertension in HFpEF patients, suggesting systemic pathophysiological differences involving proliferative and mitochondrial pathways.
Effect estimate: Fold-Change 2.1
p-value: p=1.83 x 10^-5
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.
Arwood et al. (Fri,) conducted a observational in Heart failure with preserved ejection fraction (HFpEF) and pulmonary hypertension (n=64). Combined pre- and post-capillary pulmonary hypertension (CpcPH) vs. Heart failure without pulmonary hypertension was evaluated on Differential gene expression (ID2) (Fold-Change 2.1, p=1.83 x 10^-5). ID2 gene expression was significantly upregulated (fold-change 2.1) in peripheral blood mononuclear cells of heart failure patients with combined pre- and post-capillary pulmonary hypertension compared to those without pulmonary hypertension.