Telomere lengh and cellular senescence in atherosclerosis
thesisposted on 15.12.2014, 10:30 by Rachel Louise. Boultby
This study sought to investigate links between coronary artery disease (CAD) and telomere length by measuring telomere restriction fragments (TRF) in peripheral white blood cells (WBC) from subjects with CAD and also in the cells of atherosclerotic plaques. Also, an in vitro cultured endothelial cell model was designed to determine the effects of oxidative stress (via hydrogen peroxide exposure), a known risk factor for atherosclerosis, on the TRF of this cell type, which is known to play a vital role in the progression of CAD. Adjusting for age and sex, WBC from subjects with CAD had mean TRF lengths of 303bp (SD+/-90bp) shorter than those of controls (p=0.002) which is equivalent in size to individuals with no clinically overt CAD who are 8.6 years older. Plaque cells had significantly shorter TRF lengths, 6.30Kb (SD+/-0.75Kb) compared with the corresponding WBC, 7.46Kb (SD+/-0.90Kb) (P=0.001). The in vitro cell study produced results consistent with other groups in that following exposure to hydrogen peroxide, endothelial cells demonstrated senescent-like behaviour in a dose dependent manner. Telomere attrition was also tentatively linked to this exposure. In conclusion, the results from the white cell study suggests that differences seen in telomere length may be genetically mediated or due to a 'catch up' period of growth, making telomere length a possible primary factor in the disease process. Furthermore there appears to be additional site specific telomere attrition in the cells of the plaque.