Neuropilin 1 expression in human aortas, coronaries and the main bypass grafts

Abstract

OBJECTIVES: Development of intimal hyperplasia (IH) is the main pathology underlying graft failure following coronary artery bypass graft surgeries for ischaemic heart diseases, especially for great saphenous vein grafts which have a lower patency rate than internal mammary arteries. Neuropilin 1 (NRP1), which is a co-receptor for vascular endothelial growth factor found in vascular endothelial and smooth muscle cells, affects the development of IH. We examined the difference in NRP1 expression and distribution in human coronaries, aortas, mammary arteries and saphenous veins to detect a possible relation to their susceptibility to IH. METHODS: Ninety-five human vascular segments obtained from 40 patients were used for the comparison of NRP1 expression between different groups of blood vessels by western blot and real-time PCR. Additionally, staining scores were generated by computerized analysis of the microscopic images obtained after immunofluorescence and immunohistochemical staining to compare NRP1 expression patterns in endothelium, smooth muscles and adventitia in each vessel type. RESULTS: NRP1 expression in the aorta (2.03 ± 1.44) was more than twice as high as mammary artery expression (0.85 ± 0.75; n = 16, P = 0.0004); NRP1 of the latter (0.99 ± 0.91) was more than 30% greater than that of the corresponding saphenous vein (0.73 ± 0.69; n = 20, P = 0.0085). In adventitia, NRP1 receptor staining of the saphenous vein was higher (22.96 ± 8.73) than in the mammary artery (15.83 ± 7.13; n = 7, P = 0.049). Variations in NRP1 protein levels were accompanied by parallel variations in its mRNA levels (n = 15, P = 0.34). CONCLUSIONS: Autologous saphenous vein grafts, unlike internal mammary artery grafts, have lower NRP1 expression and abundant adventitial distribution of NRP1 within their walls; this may correlate with higher susceptibility to IH development.