Abstract 15922: Role of Polo-Like Kinase-1 in Intimal Hyperplasia in Saphenous Vein Graft: Potential Implication in Vein-Graft Disease
Coronary revascularization by coronary artery bypass grafting (CABG) is the choice of procedure in patients with multi-vessel or left main coronary artery disease. Concerns have been raised on the long term result of CABG using saphenous vein graft (SVG) as its patency significantly declines following surgery, compared to internal mammary artery (IMA), which is almost immune to restenosis. Proliferation of smooth muscle cells (SMCs) is the key event in the pathogenesis of intimal hyperplasia leading to SVG failure. PDGF-BB is a major growth factor released at the site of pulsatile stretch- and shear stress-induced graft injury. Here, we examined, for the first time, the expression of PLK1 and its phosphorylation/activation in isolated human bypass graft conduits. Human SV and IMA vessels were freshly collected, SMCs isolated and cultured up to 5th passage. In cultured SMCs, effect of PDGF-BB was examined on total and phosphorylated PLK1 (pPLK1) by Western blot analysis. Cell proliferation was measured using thymidine incorporation, MTT method and cell count. We found significantly higher expression of pPLK1 and total PLK1 in PDGF-stimulated SV SMCs than IMA. SV SMCs had 5-fold increase in the density of pPLK1 and had 2-fold increase in the density of total PLK1. While in the IMA SMCs, increase in pPLK1 was significantly lower than in SV SMCs. Also, this increase was not sustained. These data suggest a greater and sustained sensitivity of SV SMCs to PDGF-BB induced PLK1 activity than that of IMA. A PLK1 blocker inhibited PDGF-induced proliferation in both IMA and SV SMCs. These data demonstrate differential activity of PDGF-induced PLK1 activation, which was greater in SV SMCs than in IMA. This could explain the development of intimal hyperplasia in SV conduits than the IMA following CABG. Thus, inhibition of PLK1 could be a target in developing better therapeutic approach to prevent vein-graft disease.
Author Disclosures: S. Sur: None. S. Chen: None. J.T. Sugimoto: None. D.K. Agrawal: None.
- © 2014 by American Heart Association, Inc.