Neuropilin1as A Candidate Target For Vein Graft Gene Therapy

Background:Intimal hyperplasia (IH) is the main pathology underlying graft failure following coronary artery bypass graft surgeries (CABG) for treating ischemic heart diseases (IHD), especially for great saphenous vein (GSV) which has lower patency rate than internal mammary artery (IMA) when used as a graft. Some actions of neuropilin1(NRP1), which is co-receptor for vascular endothelial growth factor (VEGF), within vascular endothelial cells (ECs) and smooth muscle cells (SMCs) are related to development of I.H.Purpose:Review the relevant literatures to identify the impact of vein graft disease and explore its current therapies focusing upon vascular gene therapy as well as the possible roles of NRP1which may affect the intimal hyperplasic response and to analyze the patterns of NRP1expression in human aorta, coronaries and their main bypass grafts "IMA and GSV" and linking our findings to their patency ratesMethods:95vascular segments obtained from40patients were grouped into Aortas (n=35), IMAs (n=21), GSVs (n=32) and (coronaries (n=7) then were used for comparison of NRP1expression after performing western blotting and real time PCR. Immunoflourscence and histochemical staining were additionally used for NRP1localization and to generate staining scores to be used to compare NRPl expression pattern between the main vascular wall componentsResults:NRP1protein expression in human aortas and coronaries showed no difference (n=7, p=0.274) but aortas expressed higher levels of NRP1than IMAs (n=16,p=0.0004), and IMAs showed higher NRP1expression than GSVs (n=20, p=0.0085).NRP1expression in adventitia of GSVs was more than adventitia of IMAs (n=7, p=0.0491). Variations in NRP1protein levels were accompanied by parallel variations in its mRNA levels (n=15, p=0.34).Conclusion: Different levels of NRP1expression in human blood vessels and patterns of its distribution within vascular ECs, SMCs and adventitia may be related to their susceptibility to develop intimal hyperplasia; NRP1can be explored as a potential target for vein graft gene therapy.