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Karolinska institutet
Karolinska universitetssjukhuset

Ulf Hedin Group


Vascular disease is the leading cause of death and disability in the western world. In order to prevent disease development and develop preventive strategies, a complete understanding of basic cellular and molecular mechanisms is necessary. Our group has built a research platform that involves a close interaction between advanced cell and molecular biology, animal models, and patient-oriented studies. The research aims at mapping key processes in peripheral vascular disease such as thromboembolism in carotid stenosis and stroke, aortic aneurysm development, repair processes and inflammation in the vessel wall during surgical vessel reconstruction and catheter-based intervention. The group also includes translational research in traumatology.

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Research: Carotid stenosis and stroke

The project aims to identify biological processes and key molecules in atherosclerotic plaque instability that can be used to develop, among other things, biomarkers (tracers) for unstable atherosclerosis in patients at risk. The project may provide new insights into the causes of unstable atherosclerosis in patients with carotid artery stenosis and help prevent strokes.

Carotid stenosis and stroke – from molecule to man

Stroke is the third most common cause of death and disability, affecting more than 30 000 individuals in Sweden each year. When atherosclerosis plaques in the carotid artery become unstable and the narrowing ruptures, a blood clot forms that can travel to the brain, blocking blood flow, causing oxygen deprivation and leading to a stroke. Stroke can be prevented by removing plaque in the carotid artery, but this is primarily done when there is clinical evidence of plaque instability and “mini stroke” (TIA) or in patients without symptoms who are at high risk. There are currently no methods to detect and localize unstable atheromas in patients at risk and no targeted drugs to stabilize atherosclerosis and prevent stroke (Fig. 1).

Figure 1: Carotid stenosis in a patient with ischemic stroke and plaque rupture (arrow) visualized by CT angiography (arrow; CTA), with visible rupture (arrow; CEA specimen) and bleeding in the lesion (arrow; Histology).

Significance of the project

The project can provide new knowledge about the causes of unstable atherosclerosis in patients with carotid artery stenosis and lead to:

  1. improved selection of patients with high stroke risk for surgical treatment and optimized risk prevention.
  2. development of drugs that can stabilize atherosclerotic plaque and prevent stroke.
  3. improved treatment of patients with unstable atherosclerosis in other vessels, e.g. the coronary arteries of the heart relevant to myocardial infarction.

Aims of the project

The project aims to identify biological processes and key molecules in atherosclerotic plaque instability that can be used to develop:

  1. biomarkers (tracers) for unstable atherosclerosis in patients at risk.
  2. screening methods to localize unstable narrowing of the carotid artery
  3. targeted drugs that stabilize atherosclerosis and thus prevent stroke.

Work plan

The research is based on a world unique collection (Biobank of Karolinska Endarterectomies; BiKE) of more than 1400 tissue and blood samples from patients who have undergone surgery for carotid artery stenosis at our unit (Vascular Surgery Clinic, Karolinska University Hospital). The samples are analyzed with modern molecular biological techniques and cutting edge technology with the aim of clarifying which processes and molecules cause plaque instability, which leak into the blood from the narrowed artery (tracers/biomarkers) and which can thus be determined in a blood sample. Through these established collaborations, we have the opportunity to identify the genes, proteins and molecular processes that are active in unstable atherosclerosis and that can both leak into the blood as biomarkers but also form the basis for future development of drugs to counteract instability. Identified biomarkers are processed through comparisons in other patient groups and with experimental methods. Studies focused on the analysis of identified biomarkers in other cohorts (including the Swedish national study SCAPIS) have been initiated. The project also includes the development of imaging diagnostics where preoperative computed tomography images of carotid arteries are processed with software (vascuCAP) so that plaque components typical of unstable atherosclerotic plaques can be visualized and compared with both histological and biological analyses of retained plaques (Fig. 2).

Figure 2: Carotid stenosis imaged with contrast-enhanced computed tomography (CTA), visualization of the fat component (yellow; L) of the plaque after image processing with vascuCAP, and the corresponding histological image of the analyzed plaque (*= vessel lumen).

Group Leader

Ulf Hedin, Professor, ulf.hedin@ki.se

Group members

Siw Frebelius, Research coordinator, siw.frebelius@ki.se

Malin Kronkvist, Biomedical scientist, malin.kronqvist@ki.se

Mariette Lengquist, Laboratory manager, mariette.lengquist@ki.se

Selected publications

See Ulf Hedin’s publications in PubMed

About CMM

The Center for Molecular Medicine (CMM) is a foundation instituted by the Stockholm County Council (Region Stockholm). CMM is at the heart of a close partnership with the Karolinska University Hospital and Karolinska Institutet, fueling advancements in biomedical and clinical research.


Center for Molecular Medicine Foundation, org. nr. 815201-3689

Karolinska University Hospital L8:05

Visionsgatan 18

171 76 Stockholm, Sweden


Karolinska institutet
Karolinska universitetssjukhuset