Lars Melholt Rasmussen (Presenter)
Odense University Hospital
Bio: Professor in Clinical Biochemistry, University of Southern Denmark. Head of the Clinical Proteomics Laboratory at Odense University Hospital. Research Interests: Pathophysiology and biomarkers in relation to arterial diseases and diabetes.
Authorship: Lars Melholt Rasmussen
Odense University Hospital, Denmark
We have used proteome analysis on human arterial samples and find distinct protein changes in relation to diseases like diabetes, aneurysms and vascular stiffness. The observed alterations strongly support and expand our knowledge about the pathophysiology behind cardiovascular diseases.
Cardiovascular diseases like atherosclerosis, aneurysms and diabetic vascular changes are based on the development of cellular and molecular alterations in the arterial wall. These alterations lead to occlusions, stiffness or rupture at different sites in the arterial tree, which gives rise to the cardiovascular disease manifestations. Only very few studies have previously employed proteome analysis to study the pathophysiology of arterial diseases.
We have used proteome analysis on samples of human arterial tissue from our biobank, which includes arterial samples from more than 1000 individuals. We perform proteome analysis on individual samples and results from series of patients with different diseases will be presented. We have developed several extraction protocols and use LC-MSMS for analysis after iTRAQ- or TMT- for labelling as basis for quantitative analysis. We have applied these protocols to several types and amounts of arterial tissue-samples (fresh frozen, formalin fixed, +/- microdissection).
Our results show various distinct alterations of the amounts of individual, as well as groups of proteins in relation to diabetes, aneurysms and vascular stiffness. In diabetes we find that particularly proteins related to the basement membrane in the extracellular matrix are upregulated, whereas stiff arteries display alterations in small-leucine-rich-proteoglycans among other proteins, whereas we find that the growth rate of abdominal aneurysms is correlated to the arterial wall content of cytoskeletal proteins and plasma components.
Conclusions & Discussion
Our findings are good examples of the great potential of tissue proteome analysis to obtain important new pathophysiological insight in different diseases. Our findings in relation to diabetes, aneurysms and vascular stiffness have opened new perspectives in relation to understanding the development of these cardiovascular conditions. Some protein findings may in addition lead to further studies of potential biomarkers for arterial diseases.
References & Acknowledgements:
|Grants||yes||Novo Nordisk Foundation, Danish Medical Council|
IP Royalty: no
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