An ELISA for apolipoprotein M reveals a strong correlation to total cholesterol in human plasma

Abstract

Apolipoprotein M (apoM) is a 188 amino acid, 25 kDa protein belonging to the lipocalin protein superfamily. Although predominantly associated with high density lipoprotein, apoM is found in all major lipoprotein classes. To facilitate clinical studies of apoM, we have developed a sandwich ELISA for the measurement of apoM in human plasma. This method has been used to investigate normal apoM variation and to establish reference values for healthy individuals through the measurement of 598 samples from the Nordic Reference Interval Project Bio-bank and Database (NOBIDA) biobank. For women 18-49 years old, the reference interval for apoM was 0.58-1.18 mmol/l, whereas for women 501 years and for men, the reference range was 0.61-1.30 mmol/l. Correlation studies of apoM with 26 common clinical chemical analytes from the NOBIDA database revealed a marked positive correlation with plasma total cholesterol (r 5 0.52) and LDL and HDL cholesterol (r 5 0.43 and 0.36, respectively). There was no statistically significant correlation with HDL/total cholesterol ratio or body mass index. In conclusion, a sandwich ELISA for the measurement of apoM in human plasma shows that apoM concentration is strongly correlated to total cholesterol in healthy individuals.-Axler, O., J. Ahnström, and B. Dahlbäck. An ELISA for apolipoprotein M reveals a strong correlation to total cholesterol in human plasma.

The association between apolipoprotein M and insulin resistance varies with country of birth

“…In agreement with these results, we also found significantly lower levels of ApoM in participants with T2DM compared to participants with NGT; however, the difference was present only in Swedes but not in Iraqis. The mean plasma ApoM concentration in healthy individuals has been shown to be 0.9 µM [24]. In concurrence with these results, we found approximately the same levels of ApoM in Swedish participants with NGT; however, Iraqi participants with NGT had significantly lower levels of ApoM.…”

“…Furthermore, recent evidence suggests that HDL may directly contribute to the pathogenesis of T2DM through its ability to enhance pancreatic β-cell function and glucose uptake in skeletal muscles [27]. HDL levels are known to strongly correlate with ApoM [24] .…”

“…They were then centrifuged for 10 min at 4 °C and serum was aliquoted and stored at -80 °C for further use. ApoM levels were measured by a sandwich ELISA method described previously [24]. Briefly, 96-well Costar plates (Corning Inc., Lowell, MA, USA) were coated with a catching monoclonal ApoM antibody (mAb 58) and blocked with quenching buffer.…”

Structure of HDL: Particle Subclasses and Molecular Components

“…ApoM is an apolipoprotein found mainly in HDL (Axler et al 2007) which possesses an eight stranded antiparallel beta-barrel lipocalin fold and a hydrophobic pocket that ensures binding of small hydrophobic molecules, primarily sphingosine-1-phosphate (S1P) (Ahnstrom et al 2007;Christoffersen et al 2011). ApoM reveals 19 % homology with apoD, another apolipoprotein member of the lipocalin family (Sevvana et al 2009), and is synthesised in the liver and kidney.…”

Regulation of Human Apolipoprotein M Gene Expression by Orphan and Ligand-dependent Nuclear Receptors

“…Studies in humans and in mice overexpressing or lacking apoM have shown a positive association between plasma apoM levels and total as well as HDL and LDL cholesterol concentrations (21)(22)(23). Wolfrum et al (24) demonstrated that the lack of apoM expression in transcription factor-1␣/hepatocyte nuclear factor-1␣ (TCF-1␣/HNF-1␣) knock-out mice or in apoM small interfering RNA-injected mice leads to formation of larger size HDL1 particles and the disappearance of pre-␤-HDL particles in plasma suggesting that apoM may play a role in HDL remodeling, particularly with regard to metabolism of pre-␤-HDL.…”