Pregnancy-associated plasma protein-A: an emerging cardiac biomarker.
Pregnancy associated plasma protein-A (PAPP-A), originally discovered as a glycoprotein found in the serum of pregnant women, is emerging as a potential biomarker of plaque instability. It is produced by the syncytiotrophoblasts of the placenta and circulates in the form of an approximately 500 kDa heterotetramer. In addition, PAPP-A is present in the sera of men and non-pregnant women at much lower levels in the form of a homodimer, and is produced by a number of different non-placental cell types, including fibroblasts, vascular endothelial cells, and vascular smooth muscle cells. The identification of PAPP-A as a member of the metzincin metalloproteinase superfamily, its synthesis by cell types involved in atherogenesis, and its role in insulin-like growth factor-I regulation has led to the hypothesis that PAPP-A is involved in atherosclerotic plaque progression and instability. Serum PAPP-A may be a biomarker for the detection of vulnerable, unstable plaque. Although early reports appear to validate this hypothesis, adoption of PAPP-A as a clinical cardiac biomarker will need assay standardization and further clinical validation. The clinical validation will require a large and diverse patient population, a clearly defined and uniform diagnostic strategy, incorporation of multiple biomarkers in addition to PAPP-A, and measurement of outcomes data.
Thorn
Eric M
EM
Division of Cardiology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
Khan
Ijaz A
IA
D000208:Acute Disease; D000789:Angina, Unstable / Q000097:blood* / Q000175:diagnosis; D015415:Biomarkers / Q000097:blood; D003324:Coronary Artery Disease / Q000097:blood* / Q000175:diagnosis; D006801:Humans; D009203:Myocardial Infarction / Q000097:blood* / Q000175:diagnosis; D011266:Pregnancy-Associated Plasma Protein-A / Q000032:analysis*; D013577:Syndrome
D015415:Biomarkers; D011266:Pregnancy-Associated Plasma Protein-A