U240303.pdf (7.77 MB)
The role of endothelial progenitor cell in the aetiology and pathogenesis of coronary artery disease
thesisposted on 2014-12-15, 10:34 authored by Andrew Whittaker
The primary aims of the work undertaken in this thesis were to examine whether there is genetic regulation of EPC number and / or function and to determine if EPC dysfunction precedes the onset of CAD. In additional studies, the role that EPCs play in two relevant coronary pathologies - in-stent restenosis (ISR) and coronary collateralisation - was examined. Finally, an exploratory analysis was undertaken to determine if cellular senescence, assessed by telomere length, impacts on EPC function. A total of 162 subjects were studied including 24 healthy parent-healthy offspring pairs and 27 CAD parent-healthy offspring pairs for the principle objectives. The relationships between EPCs and ISR and coronary collateralisation were studied in 21 and 39 subjects, respectively. In all subjects, the number of circulating CD34+VEGFR-2+ and AC133+VEGFR-2+ EPCs, the number of EPCs grown in vitro, and the migration capacity of cultured EPCs towards VEGF were determined. There was significant correlation in the number of cultured EPCs between parents and their offspring (Healthy: R=0.492, p=0.015; CAD: R=0.751, p<0.001) Offspring of subjects with CAD had significantly higher numbers of circulating CD34+VEGFR-2+ and AC133+VEGFR-2+ cells than offspring of healthy subjects (p=0.018 and p<0.001, respectively). There was no striking relationship between EPC number or function and either ISR or degree of coronary collateralisation. Telomeres were significantly shorter in offspring of subjects with CAD than offspring of healthy subjects (5.7 +/- 0.2 kb vs 6.7 +/- 0.7 kb, p < 0.001). There was no association between telomere length and EPC function. EPC number is at least partly genetically regulated. Circulating EPC number may represent biological markers of occult vascular damage in offspring with hereditary risk of CAD.
Date of award2008-01-01
Author affiliationCardiovascular Sciences
Awarding institutionUniversity of Leicester