Abstract 1098: Deficiency of Mannose Binding Lectin is Associated with Increased Postprandial VLDL1 Despite Normal Fasting Plasma Triglycerides
Introduction: Mannose binding lectin (MBL) is one of the three initiators of complement activation of the innate immune system. MBL deficiency has been associated with the development of atherosclerosis. However, the mechanism of this relationship is unclear. Since atherosclerosis, inflammation and postprandial lipemia are linked to the complement system, we studied the effects of MBL deficiency on the metabolism of postprandial lipoproteins.
Methods: We performed an observational study in 107 volunteers of whom 23 were MBL deficient. Baseline cardiovascular risk factors were determined in all and oral fat loading tests (OFLTs) were carried out in 8 MBL deficient and 14 MBL sufficient subjects. Postprandial lipoprotein responses were calculated as area under the curve (AUC) and incremental AUC (dAUC).
Results: MBL activity in the 23 deficient subjects was (mean±SEM) 0.22±0.02 and in MBL sufficient subjects 1.38±0.09 micrograms/ml (P<0.005). There were no differences in baseline cardiovascular risk factors between MBL deficient and sufficient subjects. The occurrence of coronary artery disease in the families of MBL deficient subjects was significantly higher than in MBL sufficient subjects (50% vs. 15%; P=0.002). Postprandial TG changes were similar in the groups. Postprandially, MBL deficient subjects had 61% lower chylomicron-apoB48, 71% higher VLDL1-apoB100 and 49% higher VLDL1-TG-dAUC. MBL activity was inversely related to the postprandial VLDL1-TG increase (r= -0.58, P= 0.005). Furthermore, MBL sufficient subjects showed a normal postprandial C3 increase of 7% at 2 hours, whereas this response was absent in MBL deficient subjects.
Conclusions: The atherogenic tendency of MBL deficient subjects may in part be explained by an impaired clearance of large triglyceride-rich lipoproteins and the accumulation of their remnants. The postulated mechanism is impairment of complement activation.