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

Article

关键词: INTERNAL-MAMMARY-ARTERY;    GROWTH-FACTOR;    SAPHENOUS-VEIN;    ANGIOTENSIN-II;    PULSATILE STRETCH;    TYROSINE KINASE;    PHOSPHOLIPASE-D;    CORONARY;    P27(KIP1);    ATHEROSCLEROSIS;   

DOI  :  10.1161/01.CIR.97.2.181

来源: SCIE

【 摘 要 】

Background-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. Methods and Results-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, H-3-thymidine incorporation, or cell counting. PDGF receptor expression and autophosphorylation, regulation of mitogen-activated protein kinases (MAPKs), and cyclin-dependent kinase inhibitors (p27(Kip1) and p21(Cip1)) 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 (2X10(4)/well to 18+/-4X10(4)/well; P<.05) than in IMA (2X10(4)/well to 9+/-4X10(4)/well; P<.05) over an 8-day period. PDGF-BB (0.01 to 10 ng/mL) stimulated H-3-thymidine incorporation (1347+/-470% above control levels) and increased cell number in SV (2X10(4)/well to 5X10(4)/well: P<.05) but not in IMA. PDGF alpha- and beta-receptors were similarly expressed and were activated in both SV and IMA. PDGF-BB induced a similar MAPK activation (kinetics and maximal activity) in both SV and IMA cells but increased MAPK protein level only in SV. Furthermore, PDGF-BB markedly downregulated the cell cycle inhibitor p27(Kip1)) in SV, but this was much less pronounced in IMA. Conclusions-SMCs from SVs exhibit enhanced proliferation compared with IMA in spite of functional growth factor receptor expression and MAPK activation. However, PDGF increased MAPK protein level only in SV and downregulated cell cycle inhibitor (p27(Kip1)) more potently in SV than in IMA. This may explain the resistance to growth stimuli of IMA SMCs and may contribute to the longer patency of arterial versus venous grafts.

【 授权许可】

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