No conflicts of interest were declared.
Hepatocyte growth factor and c-Met expression in pericytes: implications for atherosclerotic plaque development†
Article first published online: 3 APR 2007
Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The Journal of Pathology
Volume 212, Issue 1, pages 12–19, May 2007
How to Cite
Liu, Y., Wilkinson, F., Kirton, J., Jeziorska, M., Iizasa, H., Sai, Y., Nakashima, E., Heagerty, A., Canfield, A. and Alexander, M. (2007), Hepatocyte growth factor and c-Met expression in pericytes: implications for atherosclerotic plaque development. J. Pathol., 212: 12–19. doi: 10.1002/path.2155
- Issue published online: 26 APR 2007
- Article first published online: 3 APR 2007
- Manuscript Accepted: 4 FEB 2007
- Manuscript Revised: 1 FEB 2007
- Manuscript Received: 5 OCT 2006
- The Universities UK
- The University of Manchester, UK
- hepatocyte growth factor;
Intraplaque neovascularization contributes to the progression of atherosclerosis. Our aim is to understand the mobilization of cells and factors involved in this process. We investigated the localization of hepatocyte growth factor (HGF) and its receptor, c-Met, in human atherosclerotic plaques, together with the effects of HGF on pericyte migration in vitro. Atherosclerotic femoral arterial segments were collected and analysed from 13 subjects who were undergoing lower limb amputation. Pericytes were identified in human lesions using a 3G5 antibody. Immunohistochemical analysis localized HGF mainly around microvessels, in association with some, but not all, CD31-positive endothelial cells. c-Met expression was mainly associated with smooth muscle cells and pericytes, around some, but not all, microvessels within the atherosclerotic lesions; no detection was apparent in normal internal mammary arteries. Using RT–PCR, we demonstrated expression of HGF and c-Met in a rat pericyte cell-line, TR–PCT1, and in primary pericytes. HGF treatment of TR-PCT1 cells induced their migration, but not their proliferation, in a dose-dependent manner (10–100 ng/ml, p < 0.01), an effect mediated by activation of the serine/threonine kinase Akt, shown by western blot analysis. Treating the cells with the PI3K inhibitors Wortmannin (0.1 µM) or LY294002 (10 µM) abolished these effects. This work demonstrates the expression of c-Met and HGF in human atherosclerotic arteries, in association with SM-actin-positive cells and CD-31-positive cells, respectively. HGF induces pericyte migration via PI3-kinase and Akt activation in vitro. HGF and c-Met may be involved in neovascularization during plaque development, and may recruit pericytes to neovessels. Since pericytes are thought to mechanically stabilize new blood vessels, these factors may function to protect against haemorrhage. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.