| Title: | The role of Id genes on pulmonary hypertension development in left heart failure |
| Journal: | American Heart Journal Plus Cardiology Research and Practice |
| Published: | 1 Jan 2026 |
| DOI: | https://doi.org/10.1016/j.ahjo.2025.100692 |
Publication 16897
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Abstract
Objective To investigate the role of Id genes in the development of pulmonary hypertension (PH) in heart failure (HF) and evaluate genetic variants of the ID genes associated with HF-PH. Design Experimental study using an AKR/J mouse model of HF-PH and a genetic association study using the UK Biobank cohort. Setting Laboratory animal study and population-based cohort study. Participants AKR/J mice with HF-PH and participants with HF from the UK Biobank cohort. Interventions Administration of tacrolimus (Id signaling inducer) in the mouse model. Main outcome measures Tissue-specific gene expression of Id1, Id2, and Id3 in HF-PH mice; severity of HF-PH after tacrolimus treatment; associations of single nucleotide polymorphisms of ID1, ID2, and ID3 with PH development and mortality in participants with HF. Results Id1 was upregulated in the left ventricle (Fold Change (FC) = 1.65; P = 3.0 × 10−4) of HF-PH mice. In adipose tissue, Id1 and Id3 were (FC = 0.33; P = 5.2 × 10−3 and FC = 0.50; P = 0.01, respectively), while Id2 was upregulated (FC = 1.78; P = 7 × 10−4). Tacrolimus worsened PH and diastolic dysfunction, upregulating only Id2 in adipose tissue. In the clinical cohort, rs7425561 and rs10174593 (expression quantitative loci for ID2) trended toward reduced risk of PH in HF and all-cause mortality in participants with HF-PH. Conclusion The results suggest ID1, ID2, and ID3 are involved in HF-PH pathogenesis, but more research is needed to characterize their exact role.</p>
4 Authors
- Christelle Lteif
- Paula Wachs
- Ravindra K. Sharma
- Julio D. Duarte
1 Application
| Application ID | Title |
|---|---|
| 97332 | Clinical and genetic association studies of the development, treatment, and prognosis of heart failure -related cardiovascular diseases |
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