C.J. Zuurbier MEng PhD

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C.J. Zuurbier MEng PhD

Position
Research Associate
Main activities
Education, Research
Specialisation
Research into cardiovascular physiology
Focus of research

Cardiovascular disease remains the number one cause of death, not only in the chronic human condition (cardiac infarction, heart failure, diabetes), but also in many acute traumatic hospital conditions (cardiac by-pass surgery, PTCI and acute myocardial infarction, cardiogenic shock, sepsis). Our research is directed at the understanding of the 1) mechanisms through which current novel succesfull diabetes medicine (SGLT2 inhibitors) reduce cardiovascular events (heart failure, diastolic dysfunction, cardiac infarction) and 2) crucial cellular mechanisms underlying death/survival programs of the heart cell in these acute traumatic hospital conditions conditions and at the development of treatments to push the cell death/survival programs into the direction of survival.


In our current models, with emphasis on its translation to the clinic and human condition (taking into account co-morbidities, drugs commonly used in human treatment and clinical relevant anesthetic regimens), we primarily focus on 1) unraveling of the working mechanisms of SGLT2 inhibitors, and 2) the decisive role that mitochondria play in the setting of cardiac death induced by periods of ischemia (lack of oxygen, blood flow). Attention is especially given to 1) empagliflozin, and 2) the glycolytic enzyme hexokinase II, of which its binding to mitochondria is highly regulated and is of paramount importance to protect mitochondria and thereby combat cardiac cell death in almost all of the above conditions.
 

 RESEARCH EMPHASIS ON:

 

A) THERAPY AGAINST INFARCT DEVELOPMENT, MITOCHONDRIA-MEDIATED CELL DEATH, AND INNATE IMMUNITY INVOLVEMENT

 

B) UNDERSTANDING INTERACTION BETWEEN DIABETES AND HEART FAILURE FOR THERAPY DEVELOPMENT

 

C) EXPERTISE CENTRE ON EX VIVO CARDIAC FUNCTION and METABOLISM (STABILE ISOTOPES) OF MOUSE HEARTS

 

D) EXPERTISE CENTRE FOR ANIMAL ANESTHESIA

 

Key publications
  • Smeele Kirsten M. A., Southworth Richard, Wu Rongxue, Xie Chaoqin, Nederlof Rianne, Warley Alice, Nelson Jessica K., van Horssen Pepijn, van den Wijngaard Jeroen P., Heikkinen Sami, Laakso Markku, Koeman Anneke, Siebes Maria, Eerbeek Otto, Akar Fadi G., Ardehali Hossein, Hollmann Markus W., Zuurbier Coert J. Disruption of Hexokinase II-Mitochondrial Binding Blocks Ischemic Preconditioning and Causes Rapid Cardiac Necrosis Circulation research 2011;108 (10):1165-9 [PubMed]
  • Wu Rongxue, Smeele Kirsten M., Wyatt Eugene, Ichikawa Yoshihiko, Eerbeek Otto, Sun Lin, Chawla Kusum, Hollmann Markus W., Nagpal Varun, Heikkinen Sami, Laakso Markku, Jujo Kentaro, Wasserstrom J. Andrew, Zuurbier Coert J., Ardehali Hossein Reduction in Hexokinase II Levels Results in Decreased Cardiac Function and Altered Remodeling After Ischemia/Reperfusion Injury Circulation research 2011;108 (1):60-U128 [PubMed]
  • Nederlof Rianne, Xie Chaoqin, Eerbeek Otto, Koeman Anneke, Milstein Dan M. J., Hollmann Markus W., Mik Egbert G., Warley Alice, Southworth Richard, Akar Fadi G., Zuurbier Coert J. Pathophysiological consequences of TAT-HKII peptide administration are independent of impaired vascular function and ensuing ischemia Circulation research 2013;112 (2):e8-13 [PubMed]
  • Nederlof Rianne, Eerbeek Otto, Hollmann Markus W., Southworth Richard, Zuurbier Coert J. Targeting hexokinase II to mitochondria to modulate energy metabolism and reduce ischaemia-reperfusion injury in heart British journal of pharmacology 2014;171 (8):2067-2079 [PubMed]
  • Baartscheer Antonius, Schumacher Cees A., Wüst Rob C. I., Fiolet Jan W. T., Stienen Ger J. M., Coronel Ruben, Zuurbier Coert J. Empagliflozin decreases myocardial cytoplasmic Na+ through inhibition of the cardiac Na+/H+ exchanger in rats and rabbits Diabetologia 2017;60 (3):568-573 [PubMed]
All Publications
Research programmes

C.J. Zuurbier MEng PhD (Cell survival mechanisms in acute and chronic cardiovascular pathology)

1) EXPLORING CANCER'S RESISTANCE AGAINST CELL DEATH TO FIGHT HEART DISEASE

The role of the glycolytic enzyme hexokinase and its binding to mitochondria in cell death in healthy, diabetic, remodelled and I/R hearts is investigated.

The underlying hypothesis is that our main energy factory, the mitochondrion, a proto-bacterium that invaded the eukaryotic cell about 2 miljard years ago, is kept in check by a protein hexokinase, that belongs to the pre-exisitng energy production pathway, the glycolysis. It is now clear that many forms of cell death are initiated by the mitochondrion, and that hexokinase may be viewed as a gatekeeper of this important energy / dead factory. Part of the resistance of cancer cell against cell death is probably due to its high (> 10 x) expression of hexokinase bound to mitochondria. We were the first to show that this protective mechanism may also be explored for the heart. In this project we explore whether ther heart can also use this protective mechanism against cell death, and whether pathologies with increased incidence of cardiac diseases can be traced down to diminished amounts of hexokinase (diabetes, heart failure, unprotected hearts)

 Collaboration: dr Rick Southworth, King's College London; dr Fadi Akar & dr C. Xie, Mount Sinai Medical Center, New York; dr Hossein Ardehali & dr R Wu, Northwestern University, Chicago; dr Otto Eerbeek, department Physiology, AMC

 

2) DIABETES AND HEART FAILURE: AMPLIFICATION THROUGH SIMILAR UNDERLYING IONIC DISTURBANCES

Diabetic patients have a 3-4 higher risk for cardiovascular diseases as non-diabetic patients. Here we explore the cellualr mechanisms for this interactions. We were able to unravel one of the underlying mechanism of the first diabetes drug class (SGLT2 inhibitors) able to reduce cardiovascular diseases in diabetes and build on this discoveries by focussing on the detrimental role of glucose and sodium in the pathology of both diabetes and heart failure. 

 Collaboration: dr Ruben Coronel, dr A baartscheer, dr J Fiolet, C Schumacher, department Cardiology, AMC

 

3) THE ROLE OF INNATE IMMUNITY IN CARDIAC INFARCT DEVELOPMENT

Inflammation and ischemie-reperfusie injury often have similar celluar trigger and effector mechanisms. In this project we examine whether and how our innate immune system (NLRP3, NLRX1) affects cardiac ischemia-reperfusion and the involvement of cardiac metabolism in these processes.

collaboration; dr Jaklien Leemans, department of Pathology

 

4) The interaction between ANESTHESIA, METABOLISM and INFLAMMATION; Optimizing Anesthesia for Animal Research

Usually, the anesthesiologist works in separate fields as the endocrinologist or the internist. However, as always, it all interacts. In this reseach line we examine how different anesthetic regimens affect metabolic (glucose, insulin, FFA) and inflammatory parameters. Our final goal is to optimize anesthetic regimens to allow high-quality animal research, with important spin-offs to the clinical arena.

Collaboration: dr W. Florijn, DEC, AMC, Diane Bakker, dr. S Houten, Lab. Genetic Metabolic Diseases

Faculty
N.C. Hauck PhD
Prof. M.W. Hollmann MD PhD
Prof. N.P. Juffermans MD PhD
Prof. B. Preckel MA MD PhD

Postdocs
E. Gürel

PhD Students
G.M. Balestra MD
D. Brevoord MD
B. Ergin MSc
L. Uthman
Y. Xiao PhD
H. Zhang MSc

Others
D. Bakker BSc
A. van Galen

Prof. M.J. Schultz MD PhD (Prevention and treatment of organ failure in intensive care medicine)

Prof. M.W. Hollmann MD PhD (Organprotection)

J. Horn MD PhD (Neurology on the Intensive Care Unit)

Prof. N.P. Juffermans MD PhD (Pathogenesis and treatment of organ failure in the critically ill)

Prof. B. Preckel MA MD PhD (Patient safety, procedural sedation, cardiovascular protection, optimizing perioperative metabolism, cerebral perfusion, Wireless Monitoring)

Current research funding
  • Boehringer Ingelheim International GmbH
  • European Foundation for the Study of Diabetes