Academisch Medisch Centrum Universiteit van Amsterdam

• Pathogenesis of atherosclerosis
• Treatment of increased cardiovascular risk

Biography John J.P. Kastelein

John J.P. Kastelein (1954) is Professor of Medicine and chairman of the Department of Vascular Medicine at the Academic Medical Center (AMC) of the University of Amsterdam, where he holds the Strategic Chair of Genetics of Cardiovascular Disease.

He received his medical degree in Amsterdam in 1980 where he subsequently received specialty training in internal medicine. Then, between 1986 and 1988, he was trained in medical genetics, lipidology and molecular biology at the University of British Columbia, Vancouver under the guidance of Prof.Dr. M.R. Hayden.
Upon his return to the Netherlands, he was awarded a doctorate (Cum Laude) and in 1989 he founded the Lipid Research Clinic at the Academic Medical Centre in Amsterdam, which is currently serving as a tertiary referral centre for over 5000 patients each year and has become part of the department of Vascular Medicine.

In 1995, Dr. Kastelein set up a foundation for the active identification of patients with classical familial hypercholesterolaemia (FH) in the Netherlands (StoeH), for which he currently holds a position in the board of directors. This program has now been fully institutionalized and is operational under supervision of the RijksInstituut voor Volksgezondheid en Milieu (RIVM) and financially supported by the Ministry of Health with a total grant of approximately 30 million Euros. Since its inception, the StoeH has found over 12.000 individuals for whom a molecular diagnosis of FH could be made. The subsequent improvement of the treatment of these FH carriers has saved many lives, as published in Lancet in 2001 and very recently in the British Medical Journal in 2008.

In 1997 and 1998 he served a visiting Professorship at the Center for Molecular Medicine and Therapeutics at the University of British Columbia, Vancouver, Canada. In these years, Dr. Kastelein was a co-founder of Xenon Genetics Inc., a drug discovery company that has now changed its name into Xenon Pharmaceuticals Inc. and is based in Vancouver, Canada.

Dr. Kastelein is president of the Dutch Atherosclerosis Society (DAS) and chairs the National Scientific Committee on Familial Hypercholesterolemia (EHC). He also is a member of the Royal Dutch Society for Medicine & Physics, the Council for Basic Science of the American Heart Association and the European Atherosclerosis Society. He also is a boardmember of the International Task Force for CHD Prevention and was recently appointed to the Executive Board of the International Atherosclerosis Society (IAS).

Professor Kastelein was also one of the founders of Amsterdam Molecular Therapeutics Inc. (AMT), a gene therapy company based on the concept of gene replacement in hereditary lipoprotein disorders. AMT has recently (summer 2007) enjoyed a successful Initial Public Offering (IPO) at EuroNext in Amsterdam. The results of the first successful human gene therapy trial were widely publicized in the media and are published in ATVB in 2008.

Professor Kastelein’s current research interests can be found in the etiology, diagnosis, prevention and treatment of hypertriglyceridaemia, hypercholesterolaemia and low HDL cholesterol, all conditions associated with atherosclerosis and cariovascular disease.
He has published over 540 research papers in peer reviewed journals, including Nature Genetics, Lancet, New England Journal of Medicine, JAMA and Circulation and has a Hirsch index of 55.

Dr. Kastelein is an investigator of the Bloodomics and CardioGenics consortia, two large European Union supported endavours under the Framework Programme 7, that aim to elucidate the molecular basis of atherosclerosis and premature coronary disease.

Besides the scientific programmes aimed at the etiology of atherogenesis, Dr. Kastelein also serves on a number of executive and steering committees of large intervention studies, including the IDEAL, TNT, CAPTIVATE, ENHANCE, ILLUMINATE, JUPITER, RADIANCE and numerous others of which TNT (2005), RADIANCE 1 (2007), ENHANCE (2008) and JUPITER (2008) are published in the New England Journal of Medicine, IDEAL (2006) in JAMA and RADIANCE 2 (2007) in Lancet.

Since recently, Dr. Kastelein has developed the use of non-invasive B-mode ultrasound as well as Nuclear Magnetic Resonance (MRI) studies of the carotid arteries for the diagnosis and assessment of novel treatments for atherosclerosis. This has lead to the recognition of the AMC as the world-wide leading center for this technique which has recently been exported to a substantial number of academic sites throughout Europe. This has culminated in the set up of NICE, Network of Imaging Centers in Europe of which Dr. Kastelein is the director. Dr. Kastelein’s achievements in this field are internationally recognized by numerous invited reviews on this subject.

He has directed 36 postdoctoral theses and currently, he heads a team of 6 internists, 6 postdoctoral fellows, 26 MD PhD students, and a large number of laboratory technicians and clinical trial / study coordinators

Since lowering systemic risk factors can only prevent 35% of cardiovascular events, novel interventions are needed. Two approaches are being pursued:
1. Directly increasing vessel-wall resistance against atherogenic insults.
2. Identifying inflammation-modulating pathways to attenuate atherogenesis

With respect to the first, efforts are being made to target the endothelial glycocalyx as therapeutic target.

With respect to the second, HDL-increasing agents are being evaluated as novel targets to attenuate pro-inflammatory changes.

Themes: Metabolic Disorders, Cardiovascular Diseases