Galectin-1 Is a Marker but Not a Mediator of Heart Failure With Preserved Ejection Fraction.

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 () 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 (=0.022) and in patients with heart failure (<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;<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<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.