Purpose To investigate the role of pregnancy-associated plasma protein A (PAPP-A), a novel marker of atherosclerotic plaque activity, in the progress of injured-restenosis and atherosclerosis, and the relationship between the expression of PAPP-A and inducible nitric oxide synthase (iNOS) in the wall of coronary artery.
Methods The balloon injury procedure was done in the coronary arteries of 5 male pigs (injury group), and the artery segments were harvested in 28d after balloon injury. The expression of PAPP-A and iNOS were detected in the wall of coronary arteries by the means of immunohistochemical study and reverse transcription-polymerase chain raction. Expression of PAPP-A and iNOS were also detected in coronary artery wall of four pigs fed a high-cholesterol atherogenic diet for 15 weeks (CHOL group).
Results A marked increase in PAPP-A-positive cell number of the injury group was seen compared with the CHOL group, both in medial smooth muscle cells (PAPP-A staining: 33.2±2.9 vs 5.5±2.8, p<0.05) and neointimal (intimal) cells (PAPP-A staining: 28.3±3.1 vs 3.8±2.4, p<0.05); while iNOS-positive cell number decrease, only in neointimal (intimal) cells (iNOS stain: 1.1±0.3 vs 18.4±4.2, p<0.01). The expression of PAPP-A mRNA was higher in the injury group, compared with the CHOL group (0.81±0.08 vs 0.54±0.13, p<0.05), but nearly no expression in “normal” control vessel segements (0.03±0.01); while iNOS mRNA was lower in the injury group (0.18±0.09 vs 0.62±0.13, p<0.05).
Conclusion PAPP-A plays role in the progress of early atherosclerotic lesions and restenostic lesions.