This project aims to investigate the role of Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) in human heart failure by addressing two key questions:
1. Are there genetic polymorphisms in TREM2 that correlate with the incidence or severity of heart failure?
2. Does circulating soluble TREM2 (sTREM2), as captured in UK Biobank proteomic datasets, associate with heart failure incidence or severity?
Objectives:
* To identify and characterize TREM2 genetic variants associated with heart failure phenotypes within the UK Biobank cohort.
* To evaluate associations between sTREM2 levels, derived from stored proteomic data, and heart failure diagnosis, subtype, and clinical outcomes.
* To integrate genetic and proteomic data to explore whether TREM2-related pathways contribute to the pathophysiology of heart failure in humans.
Scientific Rationale:
Preclinical studies from our group show that cardiac macrophage TREM2 expression and soluble TREM2 are elevated in a murine model of heart failure with preserved ejection fraction (HFpEF), and that Trem2 deletion exacerbates the disease phenotype. These findings suggest a protective role for TREM2 in cardiac remodeling and inflammation. However, its relevance to human heart failure remains uncharacterized. Leveraging the UK Biobank’s extensive genomic, proteomic, and phenotypic resources provides a unique opportunity to investigate the translational significance of this pathway in a large, well-characterized population. Demonstrating a genetic or biomarker-based link between TREM2 and heart failure would not only advance understanding of immunometabolic regulation in cardiac disease but also highlight TREM2 as a potential therapeutic target. As TREM2 is already under investigation in other disease areas, such findings could accelerate drug repurposing efforts for heart failure.