Andrietta Sofie Grentzmann

What is the title of your thesis?

''The Pyruvate Dehydrogenase Kinase/Pyruvate Dehydrogenase Axis in Cardiovascular Diseases: from Cellular Mechanisms to Therapeutic Implications''.

At which department and/or research unit did you complete your PhD?

Department of Molecular Medicine, Cardiovascular and Renal Research.

Who was your principal supervisor?

Professor Daniel F. J. Ketelhuth, SDU.

What question did you aim to answer with your thesis?

Cardiovascular disease is often caused by atherosclerosis, where cholesterol accumulates in the vessel wall and drives chronic inflammation. Over time, this can lead to plaque formation and, in some cases, the development of abdominal aortic aneurysm (AAA), a dangerous enlargement of the abdominal aorta with a risk of rupture.

Emerging research suggests that disease progression is influenced by cellular metabolism and inflammatory activity. In this PhD project, I investigated the role of the so-called PDK/PDH axis, which regulates cellular metabolism, in immune cells and smooth muscle cells in atherosclerosis and AAA.

What did you find?

Using laboratory experiments and mouse models, we found that changes in PDK1 in immune cells can influence the development of atherosclerosis, whereas similar changes in smooth muscle cells did not have the same effect.

In addition, treatment with dichloroacetate (DCA), which inhibits PDK, helped preserve vascular structure and reduced the development of AAA, partly by lowering inflammation and the recruitment of immune cells.

Overall, the findings suggest that altered immunometabolism plays an important role in these diseases and may represent a new target for future treatment.

How did you do it?

The project used laboratory experiments on cells, analyses of human tissue, and animal studies with genetically modified mice. In addition, drug treatments and molecular analyses were applied to investigate cellular metabolism and inflammation.

How can your research be applied (in the clinic, society, etc.)?

Cardiovascular disease affects more than 500 million people worldwide, with atherosclerosis as the most common cause. The findings from this PhD project may help develop new treatments for atherosclerosis and AAA by targeting cellular metabolism (the PDK/PDH axis).

In the long term, this could improve prevention of disease progression, reduce vascular inflammation, and thereby lower the risk of serious complications and death.

From a societal perspective, it may also help reduce the overall disease burden and the need for surgical treatment.