AbstractsBiology & Animal Science

Peripheral blood derived cells and angiogenesis in cardiovascular disease

by S. Post

Institution: Universiteit Utrecht
Year: 2009
Keywords: Geneeskunde; blood cell; myocardial infarction; angiogenesis; atherosclerosis; magnetic resonance imaging; percutaneous intervention; vessels; endothelial cell; neovascularisation; HMG-CoA reductase inhibitors
Record ID: 1251300
Full text PDF: http://dspace.library.uu.nl:8080/handle/1874/36950


Patients suffering from myocardial infarction (MI), atherosclerosis and Hereditary Hemorrhagic Telangiectasia type 1 (HHT-1) all have diseased and dysfunctional blood vessels. Cardiovascular repair in these diseases occurs not only locally, but also peripheral blood (progenitor) cells and cytokines/growth factors positively contribute to repair of malfunctioning tissue. In this thesis several aspects of cardiovascular repair have been explored. First, we show that in MI patients relatively large infarctions or unfavorable hemodynamic conditions result in increased progenitor cell mobilization and pro-angiogenic cytokine/growth factor levels in the circulation. Secondly we show that, in MI and HHT-1 patients, homing of (progenitor) cells from the peripheral blood to an infarct area is stimulated by low levels or inhibition of the endopeptidase CD26. Furthermore, in MI patients, low CD26 levels are associated with an improved cardiac function and inhibition of CD26 on (progenitor) cells improved their homing. CD26 inhibition may therefore improve cardiac outcome. In a clinical pilot trial, we furthermore investigated whether pre-medication with atorvastatin in ST-elevated-MI reduces reperfusion damage. We did not find any effects of pre-treatment with atorvastatin on cardiac function, microvascular perfusion or MI size. Finally, we show that in atherosclerotic plaques with a relatively large number of microvessels, high levels of Angiopoietin-2 are found. These high Angiopoietin-2 levels may result in leaky microvessels and subsequent plaque destabilization. Taken together, the results presented in this thesis show that MI results in mobilization of (progenitor) cells and production of high levels of pro-angiogenic cytokines/growth factors, which may improve cardiovascular repair. Furthermore, our results suggest that CD26 inhibition is a promising tool to increase homing of systemically available cells which may have beneficial effects on cardiovascular repair and function, but a clinical trial is needed to demonstrate this.