Abstract
Plasma leucine-Rich α-2-glycoprotein 1 (LRG1) is an innovative biomarker for inflammation and angiogenesis. Many adverse pathophysiological changes including inflammation, atherosclerosis, and premature mortality is associated with End-stage renal disease (ESRD). However, whether levels of plasma LRG1 correlate with the co-morbidities of ESRD patients is unknown. Plasma LRG1 and high-sensitivity C-reactive protein (hsCRP) were analyzed by ELISA in 169 hemodialysis patients from the Immunity in ESRD (iESRD) study. Patient demographics and comorbidities at the time of enrollment were recorded. Peripheral blood monocyte and T cell subsets were assessed by multicolor flow cytometry. In the univariate analysis, a higher level of LRG1 was associated with the presence of cardiovascular disease (CVD) and peripheral arterial occlusive disease (PAOD). In multivariate logistic regression models, higher LRG1 tertile was significantly associated with PAOD (odds ratio = 3.49) and CVD (odds ratio = 1.65), but not with coronary artery disease, history of myocardial infarction, or stroke after adjusting for gender, diabetes, hemoglobin, albumin, calcium-phosphate product, and level of hsCRP. In addition, the level of LRG1 had a positive correlation with IL-6, hsCRP, and also more advanced T cell differentiation. The association suggests that LRG1 participates in the progression of atherosclerosis by inducing inflammation. Therefore, the role of LRG1 in coexisting inflammatory response should be further investigated in the pathogenesis of cardiovascular morbidity and mortality in patients with ESRD.
Highlights
Plasma leucine-Rich α-2-glycoprotein 1 (LRG1) is an innovative biomarker for inflammation and angiogenesis
We found higher LRG1 tertile to be significantly associated with peripheral arterial occlusive disease (PAOD) (p for trend = 0.007*, odds ratio = 3.49), cardiovascular disease (CVD) (p for trend = 0.010*, odds ratio = 1.65), coronary artery disease (CAD) (p for trend = 0.010*, odds ratio = 1.34,), but not with history of myocardial infarction (MI) or stroke
We successfully demonstrated strong association between high plasma LRG1 with systemic inflammation and increased risk for PAOD and CVD in End-stage renal disease (ESRD) patients from the iESRD cohort
Summary
Plasma leucine-Rich α-2-glycoprotein 1 (LRG1) is an innovative biomarker for inflammation and angiogenesis. A higher level of LRG1 was associated with the presence of cardiovascular disease (CVD) and peripheral arterial occlusive disease (PAOD). Cardiovascular mortality in patients with end-stage renal disease (ESRD) remains the leading cause of death[1,2]. Two types of PRRs, Toll-like receptors (TLRs) over the cell surface and inflammasomes in the cytoplasm can interact with endogenous ligands They are involved in the development of pro-inflammatory microenvironment in renal failure. Activation of these innate immune pathways is www.nature.com/scientificreports associated with hypertension, development of atherosclerotic plaques, vascular calcification and clinically significant cardiovascular diseases in CKD patients. The level of LRG1 protein was two-times higher in ESRD patients treated with hemodialysis than in CKD stage 2/3 patients. We investigate the association between plasma LRG1 with cardiovascular comorbidities in hemodialysis patients of iESRD cohort
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