Dr. ir. C.J. Zuurbier PhD

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Dr. ir. C.J. Zuurbier PhD

Position
Scientific staff member (UD)
Main activities
Research, Teaching
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 crucial cellular mechanisms underlying death/survival programs of the heart cell in these 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 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 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 KMA, Southworth R, Wu R, Xie C, Nederlof R, Warley A, Nelson JK, van Horssen P, van den Wijngaard JP, Heikkinen S, Laakso M, Koeman A, Siebes M, Eerbeek O , Akar FG, Ardehali H, Hollmann MW, Zuurbier CJ, Disruption of Hexokinase II-Mitochondrial Binding Blocks Ischemic Preconditioning and Causes Rapid Cardiac Necrosis. CIRC RES 2011;108 (10):1165-9 [PubMed]
  • Wu R, Smeele KM, Wyatt E, Ichikawa Y, Eerbeek O , Sun L, Chawla K, Hollmann MW, Nagpal V, Heikkinen S, Laakso M, Jujo K, Wasserstrom JA, Zuurbier CJ, Ardehali H, Reduction in Hexokinase II Levels Results in Decreased Cardiac Function and Altered Remodeling After Ischemia/Reperfusion Injury. CIRC RES 2011;108 (1):60-U128 [PubMed]
  • Nederlof R, Xie C, Eerbeek O , Koeman A, Milstein DMJ, Hollmann MW, Mik EG, Warley A, Southworth R, Akar FG, Zuurbier CJ, Pathophysiological consequences of TAT-HKII peptide administration are independent of impaired vascular function and ensuing ischemia. CIRC RES 2013;112 (2):e8-13 [PubMed]
  • Nederlof R, Eerbeek O , Hollmann MW, Southworth R, Zuurbier CJ, Targeting hexokinase II to mitochondria to modulate energy metabolism and reduce ischaemia-reperfusion injury in heart. BRIT J PHARMACOL 2014;171 (8):2067-2079 [PubMed]
  • Baartscheer A, Schumacher CA, Wüst RCI, Fiolet JWT, Stienen GJM, Coronel R, Zuurbier CJ, 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

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
Dr. ir. C.J. Zuurbier PhD
Dr. N.C. Hauck-Weber PhD
Prof. dr. M.W. Hollmann MD PhD
Prof. N.P. Juffermans MD PhD
Prof. dr. B. Preckel MA MD PhD

Postdocs
E. Gürel

PhD Students
Drs. L. Uthman
Y. Xiao PhD
G. Balestra MD
Drs. D. Brevoord MD
B. Ergin MSc
H. Zhang MSc (Xi'an Jiao Tong University, China)

Others
A. Van der Graaf

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

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

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

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

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

Other research related activities
  • Contribution to training of professionals, Nederlandse Hartstichting
  • Membership of medical or scientific committee, European Society Cardiology, Working group Cellular Biology of the Heart
  • Contribution to training of professionals, University of Amsterdam
Current research funding
  • AMC
  • European Foundation for the Study of Diabetes