Plasma Concentration Of Netrin-1in Patients With Coronary Artery Disease And Its Association With Coronary Artery Stenosis

Background and objectivesCoronary artery disease (CAD) is characterized by atherosclerosis in the epicardial coronary arteries. Atherosclerotic plaques, the hallmark of atherosclerosis, progressively narrow the coronary artery lumen and impair antegrade myocardial blood flow. Atherosclerosis is a disease of chronic inflammation that is distinguished by the persistence of cholesterol-engorged macrophages in arterial plaques. These macro-phages also known as the major sources of foam cells cause expansion of the plaque through recruitment of additional leukocytes and vascular smooth muscle cells. Resolution of acute inflammation typically involves emigration of monocyte-derived cells out of the inflamed site through nearby lymphatic vessels. This process appears to be impaired in atherosclerosis and has been attributed, in part, to the cholesterol loading of macrophages which shifts these cells to a more sessile phenotype. It has been proven in vitro and in animal studies that macrophage-engorged-cholesterol in the atheroma highly expresses netrin-1resulting in the atheroma progression and thereby promotion of atherosclerosis. However studies in humans remain scarce therefore our study aimed to assess the association between plasma netrin-1level and the severity of coronary artery disease using the Gensini score system.Materials and methods Our population is composed of88patients from the department of cardiovascular disease at the second XiangYa hospital of central south university of Changsha who underwent coronary angiography (CAG). All subjects were programmed for the coronary angiography by digital subtractive angiography. The patients were classified into two groups based on their Coronary angiography results:the coronary artery disease group (n=59) composed of three subgroups (Stable angina=14, Unstable angina=26, Myocardial infarction=19) and non-Coronary artery disease group (n=29). Coronary artery disease patients were those who had greater than or equal to50%reduction in at least one main coronary artery(Left main coronary artery, Left anterior descending coronary artery, Left circumflex coronary artery, Right coronary artery), whereas non-coronary artery disease subjects had less than50%luminal narrowing of the coronary arteries on coronary angiography. Patient information, including age, gender, clinical manifestations were recorded. Peripheral blood samples were obtained from patient’s femoral arteries/veins or radial arteries before coronary angiography or emergency percutaneous coronary intervention in patients with acute myocardial infarction. The patients fasted for at least8hours before blood collection, and then routine blood, urine, serum concentrations of total cholesterol (TC), triglycerides(TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and blood glucose (FBS) were determined with the use of standard laboratory procedures. Netrin-1level was obtained using a monoclonal antibody sandwich ELISA test. All analyses were performed with the Statistical Package for Social Sciences version16.0. Clinical data and plasma netrin-1value of non-coronary artery disease (controls) were compared with those with Coronary artery disease by the use of the independent sample t-test. Category distributions were compared between groups with the Fisher exact test. One-way analysis of variance (ANOVA) least squares difference test was used to compare netrin-1concentrations among multiple Gensini score groups. Bivariate correlation analyses between the variables were performed with Pearson’s correlation analysis or nonparametric Spearman’s correlation test. A two-tailed P value<0.05was considered statistically significant.ResultsPlasma concentration of netrin-1was very low and almost undetectable in some cases. Comparing with the control group and between the different subgroups, there was no significant difference of plasma concentration of netrin-1and no significant association of netrin-1with the gender (p=0.168) and age. Unstable angina group have the highest Gensini score (47.38±40.45) whereas Stable angina group have the lowest (10.28±12.12) with a significant difference between the three groups (p=0.01). Correlation analysis between Gensini score or Netrin-lwith cardio-metabolic parameters in all the patients was performed and did not show any significant correlation between netrin-1and Gensini score (r=-0.129p=0.329). The other cardio-metabolic parameters did not also correlate neither with netrin-1or, nor with Gensini score.ConclusionOur study confirms what other studies have demonstrated previously that there is no significant difference between plasma concentration of netrin-1in patients suffering from coronary artery disease and those without the disease in spite of the important role that this protein plays in the processes of build-up and destabilization of the atheroma plaque. Netrin-1did not correlate with Gensini score and the cardio-metabolic parameters studied. These findings indicate that netrin-1can’t be currently used as a biomarker for the diagnosis of coronary artery disease. However, it keeps all its interest in the field of cardiology because it’s involved in the phenomena of build-up, destabilization and embrittlement of the atheroma plaque (this increases the risk of myocardial infarction), promotion/inhibition of angiogenesis and cardioprotection against ischemia-reperfusion injury thereby offering other interesting perspec-tives.