Cardiovascular diseases (CVDs) are mainly caused by atherosclerosis, a chronic inflammatory disease of the artery wall. We have found evidence that a small metabolic enzyme, pyruvate dehydrogenase kinase-1 (PDK1), is associated with CVD burden in humans. My project aims to systematically investigate immunometabolic reactions driven by PDK1, in immune and vascular cells, with the potential to reveal a new target for therapies or a novel biomarker for CVD disease progression and complications.
The role of pyruvate dehydrogenase kinase-1 in cardiovascular diseases
Atherosclerosis is a chronic inflammatory disease driven by maladaptive immune responses. Novel insights into immune processes have revealed that changes in intracellular metabolism can strongly affect inflammation. Pyruvate dehydrogenase kinase-1 (PDK1) has been identified as a major metabolic enzyme regulating immune cell activation. Preliminary data from Prof.Ketelhuth’s group suggest that PDK1 expression/activity is associated with symptomatic atherosclerotic disease.
In my project, I will use cell culture systems, genetically-modified animal models of disease, as well as unique human peripheral blood samples to investigate PDK1-driven mechanisms in deep detail and evaluate its potential for modulating experimental atherosclerosis, as well as its potential as a biomarker for disease progression and/or complications. Better understanding of the molecular mechanisms driving atherosclerosis will help accelerate the development of new diagnostic modalities, as well as new therapies against major life-threatening diseases, including myocardial infarction and stroke, the major cause of death worldwide.
Professor Daniel F. J. Ketelhuth, University of Southern Denmark, Department of Molecular Medicine
Associate researcher Daniel Engelbertsen, PhD, Lund University
Associate Professor Lasse Bach Steffensen, PhD, University of Southern Denmark