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Gleissner, CA; Erbel, C; Linden, F; Domschke, G; Akhavanpoor, M; Helmes, CM; Doesch, AO; Kleber, ME; Katus, HA; Maerz, W.
Galectin-3 binding protein, coronary artery disease and cardiovascular mortality: Insights from the LURIC study.
Atherosclerosis. 2017; 260(1):121-129
Doi: 10.1016/j.atherosclerosis.2017.03.031
Web of Science
PubMed
FullText
FullText_MUG
- Co-Autor*innen der Med Uni Graz
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März Winfried
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- Abstract:
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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.
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.
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).
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.
Copyright © 2017 Elsevier B.V. All rights reserved.
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