Cardiology/Cardiovascular Research Translational Studies
Department of clinical sciences Malmö
PI: Isabel Goncalves
Many vicitims of heart attacks and stroke die before reaching the hospital. The most frequent cause of myocardial infarction and stroke is the rutpure of an atherosclerotic plaque with the subsequent formation of a thrombus that occludes the vessel.
The vulnerable atherosclerotic plaque: mechanisms of development and techniques for imaging
The rupture-prone plaques, are called vulnerable plaques (VP) and usually have a large lipid and necrotic core, are rich in inflammation and are covered by a thin fibrous cap. There are currently no good techniques for the timely identification of VP. Therefore the development of biomarkers and imaging techniques that could identify individuals with VP, would allow the prevention of many of these severe symptoms, disability or death. Additionally it would also be possible to assess the effects of current or even newer treatment strategies on the plaques.
Since 2006, Prof Goncalves founded the Carotid Plaque Imaging Project (CPIP) and biobank, collecting human atherosclerotic plaques, their in vivo ultrasound images, living blood cells and blood samples of patients with carotid stenosis. Since 2017, assoc. Prof. Dias added the collection of blood from patients with aortic aneurysms and since 2018, Dr Edsfeldt founded the collection of human femoral plaques to the biobank too. This way, this biobank is one of the largest and most detailed in the world in the field of atherosclerosis and cardiovascular diseases.
The general goals of the Goncalves´ group are:
- To study the mechanisms of atherosclerosis and their time line using C14 dating method.
- To develop and evaluate a new non-invasive ultrasound-based technology to identify VP in humans.
- To examine whether there are associations between gene expression, lipidomics, extracellular matrix and inflammation in human atherosclerotic plaques (from our unique biobank) in relation to the risk of developing cardiovascular events and thus find new markers or treatment modalities.
In the Goncalves´ lab there are more PIs, besides Prof Goncalves:
Apoptosis and efferocytosis as mechanisms of impaired fibrotic tissue repair in diabetes associated vascular complications.
Type 2 diabetes (T2D) is increasing rapdily and patients suffering from T2D have a greatly increased risk to suffer from cardiovascular events due to accelerated atherosclerosis with more frequent plaque ruptures. Why atherosclerotic plaques tend to rupture more frequently in T2D is unknown. We recently provided evidence for an impaired tissue repair as potential cause. Here I aim to identify the mechanisms behind the impaired tissue repari in T2D.
Plaque vulnerability in atherosclerosis: Driven by interplay between co-stimulatory signalling and extracellular matrix?
The integrity of the extracellular matrix (ECM) - the dynamic structures making up the microenrironment around cells - is of crucial importance for the development and stability of atherosclerotic plaques. Key players in modulating inflammatory reactions in such lesions are the co-stimulatory molecules that direct the actions of immune cells. I believe that the co-stimulatory molecules are a key link between inflammation and the ECM milieu, allowing interactions between imune cells and plaque ECM to be the driving force behind atherosclerotic plaque destabilization. The aim of my research is to define how athersosclerotic plaque progression is driven via co-stimulatory molecules´ effects on ECM integrity, and my ultimate goal is to identify new drug targets and strategies to promote plaque stability.
To reach my goal I am analysing both human and mouse plaques to identify
- co-stimulatory molecules expression patterns in plaques
- how interplay between co-stimulatory moleculesand ECM components in plaqued affects plaque vulnerability, and
- the specific molelcular mechanisms that link co-stimulatory signalling and ECM turnover.
I am interested in any research topics on precision medicine. In addition to routine bioinformatic analysis, my current job is making our multi-omics data AI ready for the discovery of disease biomarkers and novel therapeutic targets. I am also conducting GWAS studies using our cohort and public summary statistics, e.g. UKB and FinnGen, to group high-risk individuals by means like polygenic risk scores and to estimate causality by Medelaian randomization. Moreover, we will explore chemical space for potential drugs.