Haematopoietic progenitor cells in carotid disease

Introduction Haematopoietic progenitor cells (HPCs) may attenuate the response to acute vascular injury by maintaining endothelial integrity and function. The aim of this study was to determine whether circulating HPC number and function, and mobilising cytokines, reflect significant carotid disease or correlate with restenosis following carotid endarterectomy (CEA). Methods Initially the assay conditions to measure HPC number and function were optimized. HPC numbers were measured by flow cytometry (CD133+ve/CD34+ve) and early colony forming unit assay (eCFU). HPC function was measured by migration assay and by staining for senescence associated B-galactosidase (SA-Bgal). HPC number and function was then measured in 62 patients undergoing CEA pre-operatively, 1 day post operatively and 6 weeks post-operatively. Restenosis was assessed by duplex scanning at 3, 6 and 12 months. The circulating profile of GM-CSF, PIGF, SDF1 and VEGF was measured by multiplex ELISA. Results HPC numbers (P<0.001) and eCFU counts (P=0.001) fell rapidly 24hrs after CEA. The percentage post-operative fall in CD133+ve/CD34+ve cell numbers negatively correlated with degree of restenosis at the 6 month scan (r= -0.38, p=0.013). The percentage fall in eCFU number negatively correlated with degree of restenosis at the 6 (R=-0.42, P=0.008) and 12 month scans(R=-0.49, P=0.026). The migration rate of HPCs isolated from pre-operative blood also negatively correlated with restenosis at the 6 (R=-0.5, P=0.009) and 12 month scans(R=-0.53, P=0.05). Pre-operative SDF1 levels correlated with falls in CD133+ve/CD34+ve number (R=0.42, P=0.044) and eCFU counts (R=0.56, P=0.004), though not with restenosis. Conclusion HPC function appears to be linked to the development of carotid artery restenosis following endarterectomy. These data support the concept that HPCs have a role in regulating remodelling of the unstable and injured arterial wall.

Name dc:type.qualificationname

Doctor of Philosophy

Level dc:type.qualificationlevel

Doctoral Thesis

Grantor dc:publisher.institution

King's College London

Year dc:date.issued

2012

Author dc:creator

• Patel, Sanjay

Advisors dc:contributor.advisor

• Smith, Alberto
• Burnand, Kevin Guiver

Language dc:language

eng

Identifier

oai:kclpure.kcl.ac.uk:studenttheses/27973516-c623-44a0-86be-75dc20b4e6fe

OAI identifier oai:identifier

oai:kclpure.kcl.ac.uk:studenttheses/27973516-c623-44a0-86be-75dc20b4e6fe