Galectin-3 binding protein, coronary artery disease and cardiovascular mortality: Insights from the LURIC study

Atherosclerosis. 2017 May:260:121-129. doi: 10.1016/j.atherosclerosis.2017.03.031. Epub 2017 Mar 23.

Abstract

Background and aims: Galectin-3 binding protein (Gal-3BP) has been associated with inflammation and cancer, however, its role in coronary artery disease (CAD) and cardiovascular outcome remains unclear.

Methods: Gal-3BP plasma levels were measured by ELISA in 2922 individuals from the LURIC study (62.7 ± 10.6 years, 62.7% male). All-cause and cardiovascular mortality was assessed by Kaplan-Meier analysis and Cox proportional hazards regression. Causal involvement of Gal-3BP was tested for by Mendelian randomization. Gal-3BP effects on human monocyte-derived macrophages were assessed in vitro.

Results: During 8.8 ± 3.0 years, 866 individuals died, 654 of cardiovascular causes. There was a significant increase in all-cause and cardiovascular mortality with increasing Gal-3BP quintiles. After thorough adjustment, all-cause mortality remained significantly increased in the fifth Gal-3BP quintile (HRQ5 1.292 (1.030-1.620), p = 0.027); cardiovascular mortality remained increased in Gal-3BP quintiles two to five (HRQ51.433 (1.061-1.935, p = 0.019). Gal-3BP levels were not associated with diagnosis and extent of coronary artery disease. In addition, Mendelian randomization did not show a direct causal relationship between Gal-3BP levels and mortality. Gal-3BP levels were, however, independently associated with markers of metabolic and inflammatory distress. In vitro, Gal-3BP induced a pro-inflammatory response in human monocyte-derived macrophages. Adding Gal-3BP levels to the ESC score improved risk assessment in patients with ESC SCORE-based risk >5% (p = 0.010).

Conclusions: In a large clinical cohort of CAD patients, Gal-3BP levels are independently associated with all-cause and cardiovascular mortality. The underlying mechanisms may likely involve metabolic and inflammatory distress. To further evaluate the potential clinical value of Gal-3BP, prospective studies are needed.

Keywords: Atherosclerosis; Biomarker; Coronary artery disease; Inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers / blood
  • Cardiovascular Diseases / mortality
  • Cause of Death / trends
  • Cells, Cultured
  • Coronary Angiography
  • Coronary Artery Disease / blood*
  • Coronary Artery Disease / genetics
  • Coronary Artery Disease / mortality
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flow Cytometry
  • Follow-Up Studies
  • Galactosephosphates / blood*
  • Galactosephosphates / genetics
  • Gene Expression Regulation
  • Germany / epidemiology
  • Humans
  • Kaplan-Meier Estimate
  • Macrophages / metabolism
  • Macrophages / pathology
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • Prospective Studies
  • RNA, Messenger / genetics
  • ROC Curve
  • Retrospective Studies
  • Risk Assessment*
  • Risk Factors
  • Survival Rate / trends

Substances

  • Biomarkers
  • Galactosephosphates
  • RNA, Messenger
  • galactitol 3-phosphate