Galectin-1 Is a Marker but Not a Mediator of Heart Failure With Preserved Ejection Fraction
Hypertension, 2026
Wassenaar J., Smart C., Fehrenbach D., Shuey M., Sangowdar P., Zhong L., Miller F., Wells Q., Huang S., Collins S., Storrow A., Miller K., Gupta D., Doran A., Madhur M.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
CVD | Pathophysiology | Plasma |  Olink Explore 3072/384 |
Abstract
BACKGROUND:
The immune system is emerging as a key player in driving cardiac remodeling in heart failure with preserved ejection fraction (HFpEF). Galectin-1 ( Lgals1 ) is a carbohydrate-binding protein that we previously identified as being upregulated in cardiac myeloid cells in a preclinical model of HFpEF. Our objective was to determine the role of galectin-1 in HFpEF in both preclinical models and clinical cohort studies.
METHODS:
Galectin-1 was measured using the Olink proximity extension assay in human cohorts. HFpEF was induced in mice with myeloid-specific and global deletion of galectin-1 and corresponding controls using the hypertensive deoxycorticosterone acetate-salt model.
RESULTS:
Plasma galectin-1 was higher in both a preclinical model of HFpEF ( P =0.022) and in patients with heart failure ( P <0.001) in the UK Biobank. In patients without heart failure, higher galectin-1 levels were associated with a greater risk for incident heart failure (hazard ratio, 3.1 for quartile 4 versus quartile 1; P <0.001). In patients with acute HFpEF, galectin-1 was positively associated with NT-proBNP (N-terminal pro-B-type natriuretic peptide), a biomarker of worse prognosis (ordinal regression P <0.001). Mice with myeloid cell or global deficiency of galectin-1, however, exhibit no difference in deoxycorticosterone acetate-salt-induced HFpEF.
CONCLUSIONS:
Greater circulating galectin-1 levels are associated with a higher risk of incident heart failure and higher NT-proBNP among patients with acute HFpEF. However, neither global nor myeloid deficiency of galectin-1 altered the cardiovascular phenotype in a preclinical model of HFpEF, suggesting that it is a marker but not a causal mediator of the disease.