The Shock research group is a multidisciplinary group within the University Medical Center Groningen (UMCG) comprising of clinician scientists and basic researchers from the Dept. of Critical Care and the EBVDT research group. Our translational research is dedicated to understanding the pathophysiology and mechanisms of SHOCK-mediated organ failure in order to improve the clinical care of critically-ill patients.
Translational studies investigating the microvasculature in Acute Kidney Injury, the Angiopoietin/Tie2 as a therapeutic target
Accumulating evidence from animal and human studies points to the involvement of the Ang/Tie system in vascular barrier dysfunction during critical illness. In this project we aim to elucidate the role of microvascular Tie2 in shock-induced Acute Kidney Injury by translating clinical observations into model systems. In addition, we are investigating the role of the Ang/Tie2 system in renal microcirculatory perfusion and integrity during cardiopulmonary bypass induced AKI. This work is done in collaboration with Prof. Dr. C Boer and Dr. C van den Brom (The Experimental Laboratory for Vital Signs (ELVIS) , VUmc Amsterdam).
The pathophysiology of human sepsis-mediated AKI
Sepsis-induced acute kidney injury (AKI) is the most common form of AKI observed in critically ill patients and is associated with high mortality despite being able to support vital organ systems in the ICU. This high mortality is partly due to our poor understanding of the
pathophysiological mechanisms of sepsis-induced AKI and as a consequence there is a lack of therapeutic options for sepsis-AKI patients. In this project, we are elucidating the consequences of sepsis-AKI by investigating kidney damage in human post-mortem kidney biopsies from sepsis-AKI patients.
Understanding microvascular endothelial cell behaviour and the effects of pharmacological intervention
Organ-specific endothelial dysfunction contributes to the development of both acute inflammatory disease as well as chronic inflammatory disorders, highlighting the importance of maintaining endothelial integrity and quiescence. Current studies focus on understanding 1) the initial cellular and molecular responses in organs to systemic inflammatory signals and how this leads to SHOCK-induced microvascular endothelial activation and inflammatory activation, and 2) In vivo microvascular segment specific gene transcription control and pharmacolomics. At present, we are focusing on the microvascular endothelial behaviour in the kidney.
The role of the microvasculature in perioperative complications
Complications after surgery become an increasingly important entity in the aging population. In recent years, the microvascular endothelium has been identified as a major player in the pathophysiology of perioperative complications. However, firstly, the underlying mechanisms of the relation between macro- and microcirculation and secondly, the molecular mechanisms of endothelial pro-inflammatory activation in complications after surgery are incompletely understood. As complications affect the benefit of surgical treatment, a better understanding of the phenotype of the microvascular endothelium is needed for the development of novel therapies and preventative strategies, and further, to develop biomarkers that reflect microvascular endothelial function in the surgical population.
Current project aims:
1) Starting a biobank with 1500 patients undergoing major surgery; collection of EDTA-plasma samples pre- and post-surgery, sublingual microcirculation (using Braedius Cytocam-IDF hand-held camera) and clinical outcome (specific registration of postoperative complications).
2) Analysis of patient plasma and its effect on of endothelial cells (inflammation, permeability, detachment) under different flow conditions (using ibidi slides).
This is a CAPE project that is being carried out as a collaboration between the RUG/UMCG (Department of Anaesthesiology, Prof. Thomas Scheeren; Department of Critical Care & Department of Pathology and Medical Biology, Dr. Matijs van Meurs, EBVDT) and the University of Oldenburg (Department of Human Medicine, Faculty of Medicine and Health Sciences, Prof. Gregor Theilmeier, Perioperative Inflammation and Infection laboratory).
Critical illness, functional decline and aging
Patients surviving critical illness have a shorter life expectancy since they lose lung, kidney and neurological physiological reserve which renders them at increased risk of organ failure. These features resemble normal aging which suggest that critical illness can lead to gradual organ function decline and premature aging. Moreover, critical illness in older patients is associated with increased mortality, higher susceptibility to infection, longer length of hospital stay and poor functional outcome in survivors. This project aims to investigate the mechanisms associated with 1) accelerated aging in critically ill patients in order to identify treatment options for restoring organ function, and 2) to understand why some patients have an increased susceptibility for developing sepsis.
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