Different proliferative properties of smooth muscle cells of human arterial and venous bypass vessels: role of PDGF receptors, mitogen-activated protein kinase, and cyclin-dependent kinase inhibitors

Circulation
Z YangT F Lüscher

Abstract

Internal mammary artery (IMA) bypass grafts have a higher patency than saphenous vein (SV) grafts. Intimal hyperplasia of SV grafts is due to smooth muscle cell (SMC) proliferation and migration. We hypothesized that different SMC growth activity exists in IMA and SV, which may explain the different patencies of arterial and venous grafts. SMCs were isolated from IMA and SV by explant culture and stimulated with serum or platelet-derived growth factor-BB (PDGF-BB). Cell growth was analyzed by explant outgrowth rate, 3H-thymidine incorporation, or cell counting. PDGF receptor expression and autophosphorylation, regulation of mitogen-activated protein kinases (MAPKs), and cyclin-dependent kinase inhibitors (p27Kip1 and p21Cip1) were analyzed by molecular techniques. SMC outgrowth from explants by serum (20%) over a 20-day period was more pronounced in SV (37+/-5%) than in IMA (4+/-3%; P<.001) of the same patients. Serum (10%) increased cell number more rapidly in SV (2 x 10(4)/well to 18+/-4 x 10(4)/well; P<.05) than in IMA (2 x 10(4)/well to 9+/-4 x 10(4)/well; P<.05) over an 8-day period. PDGF-BB (0.01 to 10 ng/mL) stimulated 3H-thymidine incorporation (1347+/-470% above control levels) and increased cell number in SV (2 x 10(4...Continue Reading

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