Relationship Between Lipopolysaccharide-binding Protein And Coronary Heart Disease

BackgroundCoronary heart disease (CHD) is a common disease and a principal cause of death in adults, it's morbility and mortality rates are increasing year by year in our country. The pathogenesis of CHD is very complicated. Inflammatory processes play a fundamental role in the pathogenesis of coronary atherosclerosis. Recently infection which cause local or system inflammation has been paid more closer attention. evidence from animal and human studies suggests that Lipopolysaccharide(LPS) which is part of Gram-negative bacteria wall play a role in inflammation and atherosclerosis.What's more,with deeping studies on Toll-like receptor-4(TLR-4) in macrophage membrane, LPS/TLR-4/NF-kB was found perhaps the major way that microorganism infection cause innate immunity activation and lead the ultimate vascular lesions. Lipopolysaccharide- binding protein (LBP) is the primary protein in this process because LBP is the first to encounter and decrease the binding energy of LPS monomers, then play a catalyst-like role in transferring LPS monomers to CD14 and TLR-4. Human plazma LBP is an acute phase reactive protein, mainly synthesized and secreted by hepatocytes.LBP belongs to Lipopolysaccharide- binding protein superfamily, 60-kDalton, membrane bound and soluble. In subclinical or chronic infections LBP plays an essential role in LPS iniciating and developing atherosclerosis.So,LBP might correlate with CHD presence and development,being an serological marker providing a mechanistic link between infection, innate immune recognition, inflammation and coronary atherosclerosis. However, the role of LBP in coronary heart disease remains to be established, especially the association of LBP with the severity and stability of coronary atherosclerosis.ObjectiveTo see whether serum LBP level correlates with the presence,stability and severity of coronary atherosclerosis and other established cardiovascular risk factors. MethodsCoronary angiography (CAG) was performed in 176 hospitalized patients who were suspected as having coronary heart disease (CHD). The severity of pathological changes of the coronary artery was assessed by the number of diseased coronary branches and Gensini's score. According to the results of CAG, the 176 patients were divided into two groups: CHD group (n=120) and non-CHD group as control (n=50). The CHD patients were further divided into subgroups according to the clinical types and the number of diseased coronary branches .All patients were devided into four groups according to Gensini's score interquartiles.Serum LBP and high sensitive C reactive protein (hsCRP) were measured by the quantitative sandwich enzyme immunoassay technique. Lipids, FPG ,blood pressure, body mass index, age, sex and prior medical histories including hypertension, diabetes mellitus and smoking status were obtained before CAG in all patients. Serum LBP , hsCRP level and other clinical characteristics were compared statistically between the subgroups, and correlation coefficient of LBP with hsCRP and other conventional risk factors for CHD was calculated, multiple stepwise regression analysis demonstrate whether plasma LBP was an independent predictor of angiographic extent of CHD. Categorical variabals are presented as percentage of patients; continuous variables are presented as mean values±SD. Skewed distribution variables are presented as median values(25th/75th interquartiles). Differences between continuous variables were tested for statistical significance by means of t tests or Mann-Whitney U test(two groups) , one-way analysis-of-variance or Kruskal-Wallis H test(multiple groups),and proportions were tested byχ2 test. We assessed associations among variables using spearman's correlation coefficient. All analyses were carried out using SPSS13.0 sofeware. P<0.05 was considered statistically significant.Results1) Plasma LBP level in CHD patients was significantly higher than that in controls 8.37(5.60～10.76) vs 12.61(9.13～17.28) mg/L( P<0.005); 2)Significant difference was found in LBP level between acute coronary syndrome and stable angina pectoris 9.98(7.39～14.36) vs 15.86(10.28～17.89) mg/L( P<0.005);In all LBP level increased with the increasing number of diseased coronary branches and Gensini's score; 3)Plasma LBP level was positively correlated with hypertension(r=0.344, P<0.001),negatively with male gender(r=-0.220, P<0.05),highly correlated with hsCRP(r=0.615,P<0.001),not correlated with other factors; 4) A significant Spearman correlation was found between LBP levels and the Gensini score of coronary artery lesions (r=0.321, P<0.001), multiple stepwise regression analysis demonstrated that plasma LBP was an independent predictor of angiographic extent of CAD (β= 0.180, P < 0.05).ConclusionPlasma LBP levels is higher in CHD patients, and has significant difference between acute coronary syndrome and stable angina pectoris, it is associated with stability of pathological changes of the coronary artery. Since LBP levels increased with the increasing number of diseased coronary branches and Gensini's score,it can be used as a parameter to predict pathological severity of coronary atherosclerosis. LBP levels positively correlated with hypertension and hsCRP, negatively correlated with male gender, not correlated with age, body mass index, smoking , diabetes mellitus ,FPG, TC,TG, LDL-C,HDL-C. It is the independent riskfactor of CHD.