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

Area of Science:

• Cardiology
• Pulmonology
• Genomics

Background:

• Heart failure with preserved ejection fraction (HFpEF) patients with pulmonary hypertension (PH) have a worse prognosis.
• Combined pre- and post-capillary PH (CpcPH) presents the highest mortality risk in HFpEF.
• The underlying mechanisms of PH in HFpEF remain largely unknown.

Purpose of the Study:

• To investigate transcriptomic associations related to PH development in HFpEF.
• To identify potential molecular markers differentiating HFpEF patients with and without PH.

Main Methods:

• Transcriptome-wide RNA sequencing on blood samples from 30 HFpEF patients (no PH, isolated post-capillary PH, CpcPH).
• Differential gene expression analysis using a quasi-likelihood method, adjusting for clinical covariates.
• Replication in 34 additional HF patients and validation in mouse models using qPCR.

Main Results:

• Six differentially expressed genes were found between CpcPH and non-PH HFpEF patients.
• The association with the ID2 gene was successfully replicated in an independent cohort.
• Id2 expression was upregulated in HFpEF mice with PH, and pathway analysis revealed proliferative and mitochondrial pathway involvement in CpcPH.

Conclusions:

• ID2 gene expression is a potential transcriptomic marker associated with CpcPH in HFpEF.
• HFpEF patients with CpcPH may exhibit systemic pathophysiological differences akin to pulmonary arterial hypertension.
• Further research into these pathways could reveal novel therapeutic targets for CpcPH in HFpEF.