Serum amyloid A1 and pregnancy zone protein in pregnancy complications and correlation with markers of placental dysfunction.

BACKGROUND: Hypertensive disorders of pregnancy (preeclampsia, gestational hypertension, and chronic hypertension), diabetes mellitus, and placental dysfunction confer an increased risk of long-term maternal cardiovascular disease. Preeclampsia is also associated with acute atherosis, lesions of uteroplacental spiral arteries resembling early stages of atherosclerosis. Serum amyloid A1 is involved in hypercoagulability and atherosclerosis, and may aggregate into amyloid, aggregations of misfolded proteins. Pregnancy zone protein may inhibit amyloid aggregation. Amyloid is involved in Alzheimer's disease and cardiovascular disease, and has been identified in preeclampsia, but its role in preeclampsia pathophysiology is unclear.

OBJECTIVES: We hypothesized that serum amyloid A1 would be increased and pregnancy zone protein decreased in hypertensive disorders of pregnancy and diabetic pregnancies, and that serum amyloid A1 and pregnancy zone protein would correlate with placental dysfunction markers (fetal growth restriction and dysregulated angiogenic biomarkers) and acute atherosis.

STUDY DESIGN: Serum amyloid A1 is measurable in both serum and plasma. In our study, plasma from 549 pregnancies (normotensive, euglycemic controls: 258; early-onset preeclampsia: 71; late-onset preeclampsia: 98; gestational hypertension: 30; chronic hypertension: 9; diabetes mellitus: 83) was assayed for serum amyloid A1 and pregnancy zone protein. Serum levels of angiogenic biomarkers soluble fms-like tyrosine kinase-1 and placental growth factor were available for 547 pregnancies, and acute atherosis evaluation for 313 pregnancies. Clinical characteristics and circulating biomarkers were compared between the pregnancy groups using Mann-Whitney U, chi-square, or Fisher's exact test as appropriate. Spearman's rho was calculated for assessing correlations.

RESULTS: In early-onset preeclampsia, serum amyloid A1 was increased compared to controls (17.1 vs. 5.1 µg/mL, p<0.001), whereas pregnancy zone protein was decreased (590 vs. 892 µg/mL, p=0.002). Pregnancy zone protein was also decreased in diabetes compared to controls (683 vs. 892 µg/mL, p=0.01). Serum amyloid A1 was associated with placental dysfunction (fetal growth restriction, elevated soluble fms-like tyrosine kinase-1 to placental growth factor ratio). Pregnancy zone protein correlated negatively with soluble fms-like tyrosine kinase-1 to placental growth factor ratio in all study groups. Acute atherosis was not associated with serum amyloid A1 or pregnancy zone protein.

CONCLUSIONS: Proteins involved in atherosclerosis, hypercoagulability, and protein misfolding are dysregulated in early-onset preeclampsia and placental dysfunction, linking them, and potentially contributing to future maternal cardiovascular disease.