Research Program: Atherosclerosis & Ischemic syndromes
It is increasingly being recognized that 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. 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 locations AMC and VUmc are actively contributing to cutting-edge breakthroughs.
Atherosclerosis, the process underlying the vast majority of cardiovascular diseases, is one of the major chronic disease burdens world-wide. Both AMC and VUmc locations 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 AMC/VUmc locations 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 fACSlities 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.
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 CoE Pulmonary hypertension & thrombosis).
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). Also, 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.
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.
Ongoing research lines within Athersclerosis & Ischemic Syndromes
PI’s and staff members of the Athersclerosis & 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 this overview and the two figures presented below.
|Carlie de Vries||AMC||Medical Biochemistry||Dia|
|Marco Götte/Cor Allaart||VUmc||Cardiology||Dia|
|Paul Krijnen/Hans Niessen||VUmc||Pathology||Dia|
|Esther Lutgens||AMC||Medical Biochemistry||Dia|
|Bert-Jan van de Born||AMC||Vascular Medicine||Dia|
|Jan van den Bosche||VUmc||Molecular Cell Biology and Immunology||Dia|
|Vivian de Waard||AMC||Medical Biochemistry||Dia|
|Menno de Winther||AMC||Medical Biochemistry||Dia|
|Jeffrey Kroon||AMC||Vascular Medicine||Dia|
Figure 1. Overview of Principal Investigators within the Athersclerosis & Ischemic Syndromes Research Program. Click on 'Dia' for more information about this research line.
Figure 2. Overview of collaboration within the Athersclerosis & Ischemic Syndromes Research Program and between Principal Investigators of Athersclerosis & Ischemic Syndromes and other ACS Research Programs. Lines represent ongoing collaboration between Athersclerosis & Ischemic Syndromes Principal Investigators. Asterisks indicate program leaders: Peter Hordijk and Jan Piek.