Serum insulin-like growth factor binding protein-1 (IGFBP-1) phosphorylation status in subjects with and without ischaemic heart disease.
ABSTRACT Insulin-like growth factor binding protein-1 (IGFBP-1) modulates the activity of IGF-I. It exists in serum as phosphorylated and less phosphorylated forms. We wished to measure serum levels of both these forms of IGFBP-1, using a novel assay, in subjects with, or without ischaemic heart disease (IHD).
We measured serum concentrations of the phosphorylated and less phosphorylated forms of IGFBP-1 in 75 subjects (36 with and 39 without IHD). Two immunoassays were used, one which detects non-, and less-phosphorylated forms (LpIGFBP-1), and another which specifically detects the serine phosphorylated form of IGFBP-1 (pIGFBP-1).
LpIGFBP-1 concentrations were significantly higher in subjects without IHD than in those with IHD (5.3+/-0.5 microg/L vs. 2.7+/-0.4 microg/L, p<0.001). pIGFBP-1 levels were also significantly higher in subjects without IHD compared to those with IHD (33.3+/-2.0 microg/L vs. 25.3+/-2.2 microg/L, p<0.01). The correlation between LpIGFBP-1 and pIGFBP-1 for all subjects was (r=0.71, p<0.001). This association was stronger in subjects without IHD (r=0.76, p<0.001) than for those with IHD (r=0.60, p<0.001). A significant negative association was observed between IGF-I and the ratio between the two forms (r=-0.45, p<0.0001). Receiver-Operating Characteristic (ROC) curve showed the highest area under the curve for LpIGFBP-1 (0.75) [95% CI: 0.63-0.86] and optimum cut-off value of 2.83 microg/L with 75% sensitivity and 74% specificity.
We propose that low serum concentrations of IGFBP-1 forms could be a marker of coronary risk, and the LpIGFBP-1:pIGFBP-1 ratio may be an index of biologically active IGF-I.
- SourceAvailable from: edrv.endojournals.orgEndocrine Reviews 01/1998; 18(6):801-31. · 14.87 Impact Factor
- Endocrine Reviews 03/1995; 16(1):3-34. · 14.87 Impact Factor
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ABSTRACT: We have determined the phosphorylation pattern of circulating insulin-like growth factor-binding protein-1 (IGFBP-1) in normal subjects and assessed how this changes in pregnancy. Two RIAs employing different monoclonal antibodies (MAbs 6303 or 6305) were used to measure IGFBP-1. In normal subjects, RIA 6303 measured 11-fold higher levels than RIA 6305 (72.8 vs. 6.6 micrograms/L; P < 0.008). However, in amniotic fluid (AF), the two assays gave similar results. Immunoprecipitation of plasma and AF with MAb 6303 and 6305 before nonsodium dodecyl sulfate-electrophoresis and Western ligand blotting revealed different IGFBP-1 isoforms and differential antibody recognition as the cause of this discrepancy. In AF, both MAbs precipitated nonphosphorylated and phosphorylated isoforms, whereas in plasma, only a single highly phosphorylated species, not seen in AF, was observed. This form of IGFBP-1 was precipitated by MAb 6303 only. During pregnancy, the phosphorylation state of IGFBP-1 in the maternal circulation was altered, as nonphosphorylated IGFBP-1 and three lesser phosphoforms were also observed. The appearance of these other variants resulted in a significant increase in IGFBP-1 measured by RIA 6305 (37, 51, and 83 micrograms/L in first, second, and third trimesters, respectively; P < 0.0005 vs. controls). The changes in IGFBP-1 phosphorylation induced by pregnancy may influence the modulatory effects of IGFBP-1 on IGF bioavailability and, hence, fetal growth.Journal of Clinical Endocrinology & Metabolism 01/1995; 79(6):1735-41. · 6.43 Impact Factor