Abstract 315: Potential Regulation of Intimal Hyperplasia by ADAM12 and Polo-Like Kinase-1 in Human Saphenous Vein Grafts in Coronary Artery Bypass Patients
Proliferation and migration of smooth muscle cells (SMCs) are the key events in the development of intimal hyperplasia, causing coronary artery bypass graft (CABG) failure. Although internal mammary artery (IMA) is comparatively immune to restenosis, saphenous veins (SV) are most commonly used bypass conduits. The underlying mechanisms that makes SV graft more prone to restenosis are not known as yet. The matrix metalloproteinases (MMPs) and kinases may be potential contributing factors in uncontrolled proliferation, migration and invasion of the graft conduit. In this study, we compared SMCs cultured from SV with IMA of the same patients undergoing CABG. The mRNA expression of polo-like kinases (PLKs), HER-2, ADAM 12L (long-form) and ADAM12S (short-form) were quantified by real-time PCR. The mRNA expression of cell proliferation related protein Ki-67 was measured in both conduits. Migration rate was determined using scratch assay. The mRNA expression of PLK-1, PLK-3, PLK-4, HER-2, ADAM 12L and ADAM12S were significantly higher in human SV SMCs compared to IMA SMCs. Also, SV SMCs showed higher proliferation and migration than IMA SMCs, which may be associated with increased expression of PLKs, ADAM 12 and HER-2. The protease domain of ADAM12 can cleave ECM substrates and cause migration. PLK1 is overexpressed in a variety of pathophysiological conditions and its expression correlates with cellular progression. In contrast, PLK-2 mRNA expression was higher in IMA SMCs compared to SV SMCs. The kinase activity of PLK-2 inhibits oncogenic transformation. Thus, overexpression of PLK 1 and ADAM12 in human SV bypass conduit may cause uncontrolled proliferation, migration and invasion leading to its increased incidence of intimal hyperplasia and vein graft failure in CABG patients.
- © 2012 by American Heart Association, Inc.