The circulating level of modified ldl and c3-convertase stabilization among patients with abdominal obesity

Abstract

Background. The abdominal obesity is associated with a low-grade chronic inflammatory status, to which the complement system is an important contributor. Recent studies documented the close association between modified low-density lipoproteins (mLDL) and the increase of C3 production in human macrophages. In several reports, C3 and the degree of C3 activation (C3a and C3a-desArg) have been linked to diabetes and cardiovascular disease (CVD). However the studies of C3-convertase functional activity haven’t been taken yet.Aim: to evaluate a potential association between mLDL level and C3-convertase stabilization of the classical pathway of complement system activation in middle-aged individuals with abdominal obesity at low cardiovascular risk.Patients and methods. A pilot study, including 45 patients without evidence of atherosclerosis at low CVD risk in the next 10 years according to SCORE, was designed. Abdominal obesity was detected according to the IDF criteria (2009). All patients underwent a comprehensive clinical evaluation with lipid profile and glucose analyzes. The level of mLDL (U) and the C3-convertase functional activity (%) - a key enzyme complex of the classical pathway complement activation, were assessed by using original techniques. Receiving data have been analyzed and compared in the total sample and separately among patients with abdominal obesity.Results. Analysis included 45 participants (mean age: 41(9) years; body mass index: 27(5) kg/m2; and 47% male). Mean lipid values were as follows: total cholesterol: 5.4 (1) mmol/l; LDL-C: 3.8 (1) mmol/l; HDL-C: 0.98 (0.3) mmol/l; triglycerides 2.5 (1.5–2.1) mmol/l. 27 (60%) participants of the sample had signs of abdominal obesity. Among them 41 % (11) with overweight, 44 % (12) with obesity. There were found significant differences in the mLDL level of patients with abdominal obesity and without it (p< 0,01). The median of mLDL level of patients with abdominal obesity was 15.25 U (12.3 – 24.6), while the median of mLDL level of patients without abdominal obesity was 9 U (5.7 – 12.4). Plasma mLDL levels were associated with smoking and triglycerides (Spearman up to 0.6, p<0.05), independently of low-density lipoprotein-cholesterol and other variables. The activity of stabilized C3-convertase was high (mean 18.5 (7.6)%) in the majority of patients (82%), independently of BMI, waist circumference, blood pressure, levels of TG, LDL-C, HDL-C and mLDL-C. No significant correlation between C3-convertase activity and lipoprotein fractions was found.Conclusion. Our findings underscore the role of mLDL in early atherosclerosis among the asymptomatic middle-age sample with abdominal obesity at low risk of CVD. The observed fact of stabilization of C3 convertase, apparently, can serve as a predictor of the autoimmune nature of abdominal obesity. One product of the enhanced C3 cleavage is C3a-desArg, which is a hormone that stimulates the acylation and triglyceride synthesis. The association between lipid homeostasis, obesity and innate immune system need to be studied in larger samples.