Pregnancy-associated plasma protein A in obese children: relationship to markers and risk factors of atherosclerosis and members of the IGF system

Abstract

Pregnancy-associated plasma protein A (PAPPA) is a large placenta-derived glycoprotein, which serves as a protease of several IGF-binding proteins (IGFBPs). In non-pregnant adults, measurable PAPPA levels were detected and have been implicated in the pathophysiology of atherosclerotic plaques. However, data in children is lacking. To study the relationship between PAPPA, markers of atherosclerosis, and members of the IGF system in pediatric obesity. Eighty-two obese and 52 nonobese children and 1-year longitudinal follow-up study for obese cohort. Outpatient 1-year intervention program based on exercise, behavior, and nutrition therapy. Changes in PAPPA levels, carotid intima media thickness (IMT), weight, blood pressure, lipids, metabolic markers, and members of IGF system. Baseline PAPPA (PAPPA(BL)) serum levels did not differ between obese and lean subjects. PAPPA(BL) correlated significantly with IGF1, IGFBP1, and serum cholesterol. During the 1-year-program mean IMT decreased from 0.66 ± 0.01 to 0.63 ± 0.01 mm (P<0.05) and PAPPA from 1.83 ± 0.12 to 1.58 ± 0.11 μU/l (P<0.00). In linear regression analysis with IMT after intervention as dependent variable, PAPPA contributed significantly to the observed variance. The longitudinal change of PAPPA correlated significantly with the change of serum triglycerides. In this cohort of obese children, PAPPA serum levels correlated significantly with other cardiovascular risk factors. The lack of a direct correlation between PAPPA and IMT suggests that the described association of atherosclerotic plaques and increased PAPPA levels might reflect an indirect mechanism of PAPPA with cardiovascular risk factors such as serum lipids rather than a direct effect on the vasculature.