OBJECTIVESerum pregnancy-associated plasma protein A (PAPP-A) is increased in acute coronary syndrome patients and related to prognosis. We investigated the effects of C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-alpha) on PAPP-A mRNA expression in monocytes.

METHODSMonocytes were isolated by Ficoll density gradient centrifugation from blood of healthy volunteers. The PAPP-A expressions at mRNA level post CRP or rhTNF-alpha stimulation were measured by RT-PCR.

RESULTSPAPP-A mRNA expression in peripheral blood monocytes increased 2 hours (0.2128 +/- 0.0136) and peaked 24 hours (0.6837 +/- 0.1360) after CRP (20 mg/L) stimulation compared with control group (0.1842 +/- 0.0101). PAPP-A mRNA expression increased rapidly, peaked 2 hours (1.2546 +/- 0.0866) and remained elevated up to 24 hours (0.8203 +/- 0.0413) after rhTNF-alpha (100 ng/ml) stimulation. The effects of CRP and TNF-alpha were dose-dependent. PAPP-A mRNA expression of monocytes were 0.2544 +/- 0.0611, 0.4177 +/- 0.1200, 0.5828 +/- 0.0152, 0.6837 +/- 0.1360 after stimulated with CRP (1, 5, 10, 20 mg/L), and 0.2424 +/- 0.1378, 0.3335 +/- 0.0196, 0.5742 +/- 0.0131, 0.6913 +/- 0.0219 and 0.8203 +/- 0.0413 after stimulated with rhTNF-alpha (5, 10, 25, 50 and 100 ng/ml). Actinomycin D, the DNA-directed RNA polymerase inhibitor, completely blocked CRP and TNF-alpha induced PAPP-A expression.

CONCLUSIONSPAPP-A mRNA expression could be stimulated by CRP and TNF-alpha in human peripheral blood monocytes which might be responsible for the increased serum PAPP-A level in patients with acute coronary syndromes.