Establishment of an in vitro model for diabetic atherosclerosis (project is finished)
With these studies we focus on the development of a model, an artificial blood vessel, mimicking the interaction between blood, the vascular endothelium and the smooth muscle under diabetic conditions.
Patients with diabetes are massively disposed to develop atherosclerosis, resulting in stroke and myocardial infarction. As the number of patients with diabetes is predicted to increase to more than 550 million within the next 20 years, it is crucial to understand why diabetes accelerates the development of atherosclerosis.
Our research has focused on biomarkers of atherosclerosis in patients with diabetes, primarily by analysing blood samples from large patient cohorts, using an epidemiological approach. So far, we have identified a number of promising biomarkers, which appears to be involved in the development of atherosclerosis. The next step is to perform these mechanistic studies, with the purpose of clarifying how these biomarkers may participate in the processes leading to atherosclerosis.
Through this model we aim to search for a better understanding of the mechanisms resulting in diabetic atherosclerosis, a knowledge that may improve its treatment and prevention. We believe that success in the studies may also provide novel insight and provide a better understanding of other diabetic complications. Importantly, our model may also be used to study new biomarkers and therefore, we believe it has a large potential within the field of atherosclerosis also in future research.
Project status at January 2017
One in three diabetic patients develops cardiac diseases. The mortality rate of their disease is almost five times higher than in non-diabetics. The reasons have yet to be identified, but diabetics’ high blood sugar level is considered to be a significant factor in the harmful effect on blood vessels. The research project aims to identify some of the mechanisms involved in arteriosclerosis in diabetics.
With the support of the Danish 3R-Center, we have developed a human cell model – a kind of artificial blood vessel – that mimics intercellular communication in the vessel wall. This affords us a Unique opportunity to investigate the importance of blood sugar for the subsequent signalling between endothelial cells and smooth muscle cells. The model system also replaces the use of animal models in our mechanistic
studies. Our studies show that endothelial cells have different responses to varying glucose levels and this change is also reflected in the muscle cells’ migration ability. In addition, the metabolic memory of endothelial cells also appears to affect/inhibit the ability of the cells to adapt to a changeable environment.
We are currently investigating the significance of the glucose-dependent change in signalling and the subsequent difference in migration ability for the development of arteriosclerosis in diabetics.
Articles
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