Major Reduction in Plasma Lp(a) Levels During Sepsis and Burns

Abstract

Abstract-Plasma levels of lipoprotein(a) [Lp(a)], an atherogenic particle, vary widely between individuals and are highly genetically determined. Whether Lp(a) is a positive acute-phase reactant is debated. The present study was designed to evaluate the impact of major inflammatory responses on plasma Lp(a) levels. Plasma levels of C-reactive protein (CRP), low density lipoprotein cholesterol, Lp(a), and apolipoprotein(a) [apo(a)] fragments, as well as urinary apo(a), were measured serially in 9 patients admitted to the intensive care unit for sepsis and 4 patients with extensive burns. Sepsis and burns elicited a major increase in plasma CRP levels. In both conditions, plasma concentrations of Lp(a) declined abruptly and transiently in parallel with plasma low density lipoprotein cholesterol levels and closely mirrored plasma CRP levels. In 5 survivors, the nadir of plasma Lp(a) levels was 5-to 15-fold lower than levels 16 to 18 months after the study period. No change in plasma levels of apo(a) fragments or urinary apo(a) was noticed during the study period. Turnover studies in mice indicated that clearance of Lp(a) was retarded in lipopolysaccharide-treated animals. Taken together, these data demonstrate that Lp(a) behaves as a negative acute-phase reactant during major inflammatory response. Nongenetic factors have a major, acute, and unexpected impact on Lp(a) metabolism in burns and sepsis. Identification of these factors may provide new tools to lower elevated plasma Lp(a) levels. (Arterioscler Thromb Vasc

Plasma Apolipoprotein(a) Co-Deposits with Fibrin in Inflammatory Arthritic Joints

“…37 This suggests that, at least in the samples examined, the elastolytic activity in synovial fluid was sufficiently inhibited by anti-proteases and/or that apo(a) is rather insensitive, in vivo, to digestion. As such, the present data are in line with our previous observation, in which we showed that no apo(a) fragments were generated in the circulation during cardiopulmonary bypass 38 or sepsis, 32 two conditions characterized by marked release of elastase by polymorphonuclear cells.…”

“…Apo(a) was quantitated by a sandwich enzyme-linked immunosorbent assay using mouse anti-apo(a) monoclonal antibodies of well-defined specificity, 31 as described. 32 small fraction (ϳ2%) of apo(a) immunoreactive material, were hardly visible on this exposure (lanes 2 and 8). The size of apo(a) in untreated synovial fluid (lanes 4 and 10) was similar to the one of full-length apo(a) in plasma.…”

“…32 Immunoblot analysis of apo(a) was performed after size-fractionation of synovial fluid and plasma proteins using a 5% sodium dodecyl sulfate-polyacrylamide gel electrophoresis 33 and immunoblotting using IgG-a5, a mouse antihuman apo(a) monoclonal antibody directed against K4-type 2. 31 This analysis was performed on untreated samples.…”

“…33 Concentrations of total cholesterol, highdensity lipoprotein (HDL)-cholesterol, triglycerides, and albumin were measured in cell-free synovial fluid and plasma samples using the Unimate5-chol (Roche, Basel, Switzerland), the HDL-kit (Behring, Deerfield, IL), the Unimate7-trig kits (Roche), and by nephelometry (Behring), respectively, as described. 32 LDL-cholesterol was calculated using the Friedewald formula. D-dimer concentration in mouse plasma was measured by a commercially available enzyme-linked immunosorbent assay kit designed for human D-dimer (Asserachrom D-Di, Diagnostica Stago, Asniè res, France), which cross-reacts with murine D-dimer.…”

Thematic review series: The Pathogenesis of Atherosclerosis. Effects of infection and inflammation on lipid and lipoprotein metabolism mechanisms and consequences to the host

“…Some studies showed that levels of Lp[a] are increased during stress (120,121), whereas others reported no changes or a reduction (122,123). These conflicting data may be attributable to the specificity of the assays used to measure Lp[a] levels or to interindividual variation in plasma Lp[a] levels in the population.…”