Galectin-3 Interacts with Vascular Cell Adhesion Molecule-1 to Increase Cardiovascular Mortality in Hemodialysis Patients.

Wen-Chin Ko,Tao-Hsin Tung,Wei-Ning Lin,Jian-Chiun Liou,Cheuk-Sing Choy,Chih-Yu Hsieh,Shu-Wei Chang,Jia-Feng Chang

doi:10.3390/jcm7100300

Abstract

Background: Interactions and joint effects of galectin-3 and vascular cell adhesion molecule 1 (VCAM-1) on risks of all-cause and cardiovascular (CV) mortality remain unclear in patients with maintenance hemodialysis (MHD). Methods: Unadjusted and adjusted hazard ratios (aHRs) of mortality risks were analyzed between higher and lower concentration groups of serum galectin-3 and VCAM-1. The modification effect between serum galectin-3 and VCAM-1 on mortality risk was investigated using an interaction product term. Results: During follow-up, galectin-3 and VCAM-1 were associated with incremental risks of all-cause mortality (aHR: 1.038 (95% confidence interval (CI): 1.001–1.077) and 1.002 (95% CI: 1.001–1.003), respectively). Nonetheless, VCAM-1 but not galectin-3 predicted CV mortality (aHR: 1.043 (95% CI: 0.993–1.096) and 1.002 (95% CI: 1.001–1.003), respectively). In the interaction analysis, patients with combined higher galectin-3 (>29.5 ng/mL) and VCAM-1 (>1546.9 ng/mL) were at the greatest risk of all-cause and CV mortality (aHR: 4.6 (95% CI: 1.6–13.4), and 4.2 (95% CI: 1.3–14.4), respectively). The interactions between galectin-3 and VCAM-1 with respect to all-cause and CV mortality were statistically significant (p < 0.01 and < 0.05, respectively). Conclusion: Galectin-3 and VCAM-1 could serve as a promising dual biomarker for prognostic assessment, considering their joint effects on pathogenesis of leukocyte trafficking and atherothrombosis.

Highlights

Galectin-3 is a versatile protein involved in pathogenesis of diverse human diseases, including complex types of cancer, sepsis, cardiovascular (CV) disease, brain injury, pulmonary disorders, fibrosis in different organs, chronic inflammation and autoimmune rheumatic diseases [1,2,3]
Unadjusted and multivariable adjusted hazard ratios of mortality risks were calculated for different categories of serum galectin-3 and vascular cell adhesion molecule 1 (VCAM-1) in the Cox regression model, including galectin-3, VCAM-1, albumin, age, C-reactive protein (CRP), normalized protein catabolic rate (nPCR), and smoking
We evaluated if the effect of galectin-3 on mortality risks was modified by VCAM-1 through incorporating an interaction term in the multivariate model

Summary

Introduction

Galectin-3 is a versatile protein involved in pathogenesis of diverse human diseases, including complex types of cancer, sepsis, cardiovascular (CV) disease, brain injury, pulmonary disorders, fibrosis in different organs, chronic inflammation and autoimmune rheumatic diseases [1,2,3]. Our previous study demonstrates that serum concentration of vascular cell adhesion molecule 1 (VCAM-1) is a strong independent predictor of CV mortality in MHD patients [5]. We aimed to explore the joint effect of serum concentrations of galectin-3 and VCAM-1 on all-cause and CV mortality in MHD patients. Interactions and joint effects of galectin-3 and vascular cell adhesion molecule 1 (VCAM-1) on risks of all-cause and cardiovascular (CV) mortality remain unclear in patients with maintenance hemodialysis (MHD). The modification effect between serum galectin-3 and VCAM-1 on mortality risk was investigated using an interaction product term. Patients with combined higher galectin-3 (>29.5 ng/mL) and VCAM-1 (>1546.9 ng/mL) were at the greatest risk of all-cause and CV mortality (aHR: 4.6 (95% CI: 1.6–13.4), and 4.2 (95% CI: 1.3–14.4), respectively). Conclusion: Galectin-3 and VCAM-1 could serve as a promising dual biomarker for prognostic assessment, considering their joint effects on pathogenesis of leukocyte trafficking and atherothrombosis

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Conclusion