Atherosclerosis & Ischemic Syndromes

The Atherosclerosis & Ischemic Syndromes Research Program focuses on atherosclerosis and atherosclerosis-induced clinical vascular syndromes in the fields of vascular medicine, cardiology, neurology and nephrology. This program recognizes that atherosclerosis is a  lipid-driven chronic inflammatory disease with detrimental effects on a variety of organ systems and aims to unravel its pathogenesis, to understand its clinical manifestations, to find novel biomarkers and to design novel therapeutics to combat atherosclerotic cardiovascular disease.

Atherosclerosis is a systemic disease with multiple common mechanisms, affecting a wide variety of organ systems. Eventually, atherosclerosis becomes clinically manifest via plaque rupture and intraluminal thrombosis leading to ‘acute’ distal ischemia.

In other cases, an obstruction of the lumen occurs due to a slowly progressing flow-limiting stenosis, causing stable angina pectoris or claudication, with consequences for the downstream circulation, such as lack of reperfusion after recanalization. In chronic occlusion, adaptation of the downstream circulation includes outgrowth of collateral vessels and angiogenesis.

Cutting-edge break-throughs to combat atherosclerosis and ischemic syndromes

While atherosclerosis is limited to the main vessels, many of the underlying alterations in endothelial biology occur throughout the arterial bed, affecting microvascular function, structure, and regulation of local perfusion, also in cases where overt atherosclerosis is absent. Such changes contribute to hypertension and chronic underperfusion such as in vascular cognitive decline.

At the distal end of the spectrum, patients with life-threatening acute ischemic syndromes are in need of both local as well as systemic treatment modalities to reduce the impact of the acute event as well as diminish the risk for future events.

Throughout all these pivotal areas, from preclinical pathophysiological research, translational imaging research all the way up to clinical trials, research groups in Amsterdam UMC are actively contributing to cutting-edge breakthroughs.

Infographics on research performed within the Atherosclerosis & Ischemic Syndromes research program:

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Aim

With currently outstanding basic, translational and clinical research in individual areas of the atherosclerotic spectrum, we aim to integrate the efforts on atherosclerosis and ischemic syndromes in a single institute which will facilitate the formation of a top-excellence center for Research, Diagnosis and Treatment of Atherosclerosis and Ischemic Syndromes in the world.

The traditional way of ‘dissecting’ the complications into organs/regions results in loss of expertise and insights for the systemic disease of atherosclerosis. Our ambition is to expand the position at the forefront of basic, translational and clinical research on atherosclerosis and (diagnosis and treatment of) ischemic syndromes within the next 5 years by aligning all research efforts on atherosclerosis and ischemic syndromes.

Synergising the currently fragmented research efforts on atherosclerosis, ageing, lipids, vascular barrier function and inflammation, adiposity, ischemia-reperfusion, arteriogenesis, novel imaging modalities, circulating cells and clinical translational research is in accordance with the multi-factorial nature of disease of atherosclerosis.

Implementing state-of-the-art technology and know-how in all of these areas for all translational atherosclerotic research will invariably result in highest quality research only in atherosclerosis, vascular adaptation and ischemic syndromes. The close collaboration between basic, translational and (key-opinion) clinical leaders in the field will provide a strong impact in this area.

Program Leaders

Young ACS

Jan Van den Bossche (VUmc) & Tom Seijkens (AMC)

Research Themes

Atherosclerosis

Atherosclerosis, the process underlying the vast majority of cardiovascular diseases, is one of the major chronic disease burdens world-wide. Both locations of Amsterdam UMC have a longstanding track record on pathophysiology of atherosclerosis in experimental models, imaging of atherosclerosis in risk groups and phase I-III therapeutic trials in patients with risk factors for overt atherosclerotic complications.

Whereas early translational atherosclerosis research is primarily focussed at AMC, the therapeutic studies in patients are performed at both locations. Further integration of the strong preclinical atherosclerosis research with the key-opinion-leaders in the clinical atherosclerosis research at Amsterdam UMC will lead to a unique setting, allowing full translational research from bench to bedside.

Combining GCP-compliant trial units and state-of-the-art imaging facilities provides a unique cardiovascular expert center with a large number of eligible patients to participate in clinical trials. The fully complementary nature of current research lines will enhance the competitiveness of the ACS.

Neurovascular Syndromes

The neurovascular research group has a strong track record in investigator-driven clinical stroke trials. Main research areas are neurovascular imaging and image-guided interventions of intracranial aneurysms and stroke including acute therapies (intravenous thrombolysis and endovascular treatment) and secondary prevention for ischemic stroke, carotid artery disease and cerebral venous thrombosis.

The group is a collaboration between the departments of neurology, (neuro)radiology and neurosurgery and is working in close collaboration with vascular surgery and vascular medicine. Translational studies are done in close collaboration with vascular medicine and Sanquin. Currently, we are one of the top 3 research groups worldwide on cerebral venous thrombosis (see also research program Pulmonary Hypertension & Thrombosis).

Aneurysms

Although an aortic aneurysm (AA) is generally clinically silent, the natural history is to grow and rupture. Population-based death rates of ruptured AA are high (50-80%). While the risk of rupture increases with the size of the AA, diameter is a poor predictor for rupture.

In the absence of pharmacotherapy, operative aortic repair is the only option to prevent excessive AA progression.:

  • We combine novel imaging technologies and biological and genetic parameters of AA patients to monitor AA behavior in time.
  • We develop personalized AA risk-management to identify patients with rapid AA growth.
  • We look for possible medical therapy to effectively reduce the AA growth-rate to eventually prevent rupture and death.
  • New minimal invasive operative techniques are developed to optimize surgical options.
  • Close collaboration within ACS exists within clinical trials (AJAX trial on endovascular versus open repair of abdominal aortic aneurysms; aortic aneurysm growth prevention and treatment).
  • Preclinical studies on genetic causes (like Marfan syndrome) of aortic aneurysms are investigated within ACS collaborations.

Coronary Ischemic Syndromes

Coronary ischemic syndromes cause death, heart failure and invalidating complaints like refractory angina pectoris and dyspnea. The arrival of percutaneous coronary intervention as well as improved pharmacotherapy has led to a decrease in mortality after myocardial infarction.

The next challenges are the prevention of ischemia-reperfusion damage and microvascular injury, the stimulation of neovascularisation and the regeneration of myocardial tissue to replace scar tissue. This asks for a translational approach, integrating intracoronary physiology, non-invasive perfusion imaging as well as genomics and transcriptomics to unravel basic mechanisms and propose new therapeutic strategies.

In chronic coronary artery disease clinical efforts aim at improving and evaluate complex transcatheter techniques for complete revascularization.

Renovascular Disease

Clinical management of renal artery stenosis has seen a major shift, after randomised clinical trials have shown no group benefit of endovascular intervention relative to optima! medical treatment.

On an individual level however endovascular intervention may result in significant improvement in blood pressure control and renal function. Together with the Departments of Vascular Medicine, Nephrology, Cardiology and Interventional Radiology, we try to translate intracoronary pressure and flow measurements to the renovascular circulation.

In collaboration with the TU Twente and Aarhus University we explore novel non-invasive methods using Computation Fluid Dynamics. On a national and European level we collaborate on efforts aimed to elucidate the genetics and improved diagnosis and treatment of fibromuscular dysplasia, a connective tissue disease of unknown origin that predominantly affects the renal arteries.

With these new techniques and collaborations we aim to further improve individualized treatment for patients with renovascular disease.

Peripheral Artery Disease

Peripheral arterial disease (PAD) is highly prevalent in the ageing population and has a clinical spectrum from asymptomatic through quality of life (Qol) limiting intermittent claudication (IC) to critical limb ischemia (CLI) with a potential loss of the affected limb.

In patients with IC we aim to optimize personalized medicine and non-invasive treatment modalities, develop shared decision making, and expand our expertise in health related Qol. In patients with CLI we aim to differentiate between those who need an intervention, and those who might fare well with conservative management by means of CT perfusion angiography and translational research.

PI's and ongoing research lines

The following PI's are member of the Atherosclerosis & Ischemic Syndromes Research Program:

Principal Investigator Location Department
Bert-Jan van den Born (program leader) AMC Vascular Medicine
Esther Lutgens (program leader) AMC Medical Biochemistry
Paul Knaapen (program leader) VUmc Cardiology
Marco Götte/Cor Allaart VUmc Cardiology
Otto Kamp VUmc Cardiology
Paul Krijnen/Hans Niessen VUmc Pathology
Jeffrey Kroon AMC Vascular Medicine
Paul Nederkoorn AMC Neurology
Jan Van den Bossche VUmc Molecular Cell Biology and Immunology
Carlie de Vries AMC Medical Biochemistry
Vivian de Waard AMC Medical Biochemistry
Menno de Winther AMC Medical Biochemistry
Coert Zuurbier AMC Anesthesiology

PI’s and staff members of the Atherosclerosis & Ischemic Syndromes Research program were invited to give a short pitch about their research, funding and future plans for the coming years. This resulted in the figure presented below and an overview along with slides by individual research lines (see Downloads). If your research is missing, please contact Isabelle Vergroesen: info@amsterdamcvs.org with the ongoing research template (see Downloads).

Overview of collaboration within the A&IS Research Program and with other ACS Research Programs. Lines represent ongoing collaboration between A&IS PI's. Asterisks indicate program leaders: Esther Lutgens, Bert-Jan van den Born and Paul Knaapen.
Overview of collaboration within the A&IS Research Program and with other ACS Research Programs. Lines represent ongoing collaboration between A&IS PI's. Asterisks indicate program leaders: Esther Lutgens, Bert-Jan van den Born and Paul Knaapen.

Downloads

ACS research lines by A&IS Principal Investigators:


Program members