Thesis defense Arwa Kohela: Protective and pathological remodeling in cardiac disease

Heart disease is the leading cause of death worldwide. In response to injury caused by for example a heart attack, the heart undergoes changes in its size, shape, structure and function, otherwise known as cardiac remodeling. These changes can contribute to the activation of the heart’s self-repair mechanisms to overcome the injury, but can also lead to the pathological progression of the disease. During her PhD, Arwa Kohela used different animal and cell culture models to study various aspects of cardiac remodeling.

Self-repair of the heart

The first part of her thesis describes her work on an important self-repair mechanism that protects the heart after a heart attack. Together with her colleagues, Kohela found that a specific gene called ZEB2 is more active after injury, which leads to an increased blood supply to the heart. Additionally, activity of ZEB2 leads to enhanced contraction of heart muscle cells. By boosting the activity of this gene, the researchers were able to protect the injured mouse heart from the detrimental effects following a heart attack. The gene therefore presents itself as a promising therapeutic candidate for patients with ischemic heart disease.

Reduce mortality rates

The second part of Kohela’s thesis focuses on the development of the genetic heart disease arrhythmogenic cardiomyopathy (ACM). She and her colleagues used human cardiac cell cultures and showed that the epicardium – the tissue layer surrounding the heart muscle – contributes to ACM in two important ways. First, the epicardium gives rise to fat and scar tissue, which replace the heart muscle. This leads to detrimental cardiac remodeling in patients and impaired heart function. Second, they showed that epicardial cells secrete certain factors that may potentially underlie heart beat irregularities and possible sudden death. Finding ways to target the epicardium may help to limit the progression of the disease and reduce mortality rates.

Clinical trials

“The work in my thesis signifies the importance of understanding the cellular and molecular changes that occur in patients with cardiac disease. Furthermore, I show how targeting key factors in such pathways holds great promise for future therapeutics,” Kohela summarizes. Most of the studies were performed using pre-clinical research models, such as mouse- and stem cell models. As a next step, she would like to validate their findings on higher animal models and move forward to clinical trials.

Long journey

“It has been a long journey with many exciting and happy times, but also stressful moments. I really enjoyed doing research and having a new challenge every day. The best times were when I obtained exciting new data, presented our findings at international meetings, and, the best of all, when papers got accepted. I loved the interaction and atmosphere within our lab. The people in the group are great and we shared many scientific and social events together. However, doing my PhD was also sometimes frustrating, for example when I tried to optimize an experiment for too long while a deadline was coming up,” says Kohela.

Research takes time

She advises future PhD students to try to be patient and to not worry too much about things not working out exactly as hoped during the first part of the trajectory. “Research takes time. Try to plan things well ahead, read a lot about the advances in the field and discuss your thoughts with your supervisors and peers.”

Due to the pandemic, Kohela cannot celebrate her defense in the way she hoped, but she will have some small gatherings with friends and family to commemorate the occasion.