Abstract and Introduction
Abstract
Background The lipocalin-2 (LCN2) cytokine, primarily known as a protein of the granules of human neutrophils, has been recently reported to be implicated in metabolic and inflammatory disorders. This study was designed to evaluate the relationship between serum LCN2 levels and coronary artery disease (CAD).
Methods Serum LCN2 levels of 261 in-patients who underwent coronary angiography were measured by sandwich enzyme immunoassay. Demographic (169 men and 92 postmenopausal women) and clinical (metabolic syndrome (MS), triglyceride (TG) and C-reactive protein (CRP) levels) characteristics were collected to assess independent factors of CAD (CAD: 188 and non-CAD: 73) and serum LCN2 levels by multiple logistic regression and multivariate stepwise regression analyses, respectively.
Results Serum LCN2 levels were significantly higher in men (37.5 (27.4–55.4) vs. women: 28.2 (18.7–45.9) ng/mL, p < 0.01) and men with CAD (39.2 (29.3–56.5) vs. non-CAD men: 32.7 (20.5–49.7) ng/mL, p < 0.05), and showed significant positive correlation with CAD in men (odds ratio = 2.218, 95% confidence interval: 1.017–4.839). Similarly, serum LCN2 levels were significantly higher in men with MS (40.2 (31.9–59.4) vs. non-MS: 32.0 (21.7–47.6) ng/mL, p < 0.01) and showed a significant positive correlation with the number of MS components (p for trend < 0.05). No significant differences or correlations were seen in women. TG and neutrophils (standard β = 0.238 and 0.173) were independent factors of serum LCN2 levels in men, and only neutrophils (standard β = 0.286) affected levels in women (all p < 0.05).
Conclusions Increased serum LCN2 levels are positively correlated with the presence of CAD and MS in a Chinese cohort.
Introduction
Coronary artery disease (CAD) is commonly encountered in long-term and urgent clinical care settings, yet high mortality and disability rates persist. The fundamental pathological change observed in CAD patients is atherosclerosis, and this cholesterol and lipid-based blockage has also been implicated in metabolic disorders and chronic inflammation.
The extensive research efforts put forth to elucidate the molecular mechanisms of CAD pathogenesis have indicated a potential role for the adipocyte-related proinflammatory cytokine lipocalin-2 (LCN2). It has also been detected in some organs with normal metabolism, including bronchus, stomach, small intestine, pancreas, kidney, prostate gland and thymus. Additionally, LCN2 can be secreted by activated neutrophils, adipocytes and macrophages. While in metabolic and inflammatory disorders, high LCN2 levels were noticed in adipocytes. Therefore, LCN2 has been characterized as a potential contributing factor to obesity, insulin resistance, hyperglycemia, chronic inflammation, apoptosis, and impaired renal function.
LCN2 exerts structural effects which can perturb normal physiological functions. For example, LCN2 complexes with matrix metalloproteinase-9 (MMP-9) and contributes to fibrosis, and this functional interaction is recognized by the alternative designation of LCN2 as the neutrophil-gelatinase associated lipocalin (NGAL). In addition, Lcn2 expression has been detected in clinical specimens of atherosclerosis plaques (particularly in the vascular endothelial cell, smooth muscle cell and macrophage components) and damaged myocardium, as well as in vitro analysis of arterial plaques. Studies in animal models have shown that murine atherosclerosis is accompanied by increased levels of serum LCN2 and that conditions of hypoxia and myocardial infarction (MI) induce Lcn2 mRNA expression. Serum LCN2 levels have also been found to be related to glucose metabolism and blood lipid composition.
In recent years, the possible association of serum LCN2 levels and CAD has been addressed by clinical trials, and studies based on Caucasian and Korean populations have suggested positive associations between expression of this multifunctional protein and development of this life-threatening disease with systemic implications. However, no study to date has assessed the relationship between serum LCN2 levels and CAD in a Chinese population. The current study was designed to investigate the serum LCN2 levels detected in Chinese patients who underwent coronary angiography (CAG) to address symptoms of chest pain or/and chest tightness and determine the independent factors of CAD and increased serum LCN2 levels.