Markers of endothelial dysfunction in the critical ill: The functional capacity of endothelial progenitor cells in sepsis. The role of endothelial progenitor cells and endothelial microparticles as biomarkers of symptomatic cerebral ischemia after acute brain injury

Datum: 29 juni 2015

Locatie: UAntwerp - Campus Drie Eiken - Building Q - Promotiezaal - Universiteitsplein 1 - 2610 WILRIJK

Tijdstip: 16 uur

Organisatie / co-organisatie: Faculty of Medicine and Health Sciences

Promovendus: Sabrina Van Ierssel

Promotor: Prof P. Jorens & Prof C. Vrints

Korte beschrijving: PhD defence Sabrina Van Ierssel - Faculty of Medicine and Health Sciences



Abstract

The endothelium is a key player in the development of secondary complications in critically ill patients such as those with sepsis and acute brain injury. As such, evaluation of the endothelial function is important as a possible prognostic marker and therapeutic target. The last decades new circulating markers, endothelial progenitor cells (EPC) and endothelial microparticles (EMP), as well as in vivo assessment techniques for endothelial function, peripheral reactive hyperemia (RHI) after arterial occlusion, have been developed.

In this thesis we evaluated these techniques for the assessment of endothelial dysfunction in critical ill patients. In severe sepsis we detected a blunted RHI coinciding with decreased markers of endothelial repair, i.e. EPC and functional capacity of circulating angiogenic cells (CAC).

Furthermore we showed a decreased number of EPC at admission in those patients with progression of organ failure during the first week. In acute brain injury we also found a decreased number of EPC immediately after the insult, together with a blunted RHI. While the RHI recovered the first 12 days after the insult, EPC remained reduced. In 3 out of 4 patients developing cerebral ischemia after the insult there was no restoration of RHI at day 12, while this was the case in all 8 patients without development of cerebral ischemia. As such we conclude that cellular markers of endothelial dysfunction are interesting prognostic markers, as well as possible therapeutic targets in the critical ill.

Although their arduous detection and lack of standardization hamper the implementation in routine clinical practice at present. Peripheral arterial tonometry, as well, is a convenient in vivo method for evaluating microvascular vasomotor function at the intensive care unit. However the underlying mechanisms for the vasomotor response measured need to be further unraveled in future studies.