RNA targets in cardiac disease

The heart has one task: circulating blood throughout our bodies. An adequate
circulation is essential for making sure all parts of our bodies receive enough
oxygen and nutrients. This, in turn, is required for our health and feeling of
well-being. Despite the importance of a healthy heart, the heart has no mechanism
to repair itself after being damaged. Even worse, a damaged heart will slowly
degrade further over time and cardiovascular disease is the leading cause of
death worldwide.
In this thesis, I describe the results of my PhD research. These results
contribute to developing novel ways to treat heart patients. My first experimental
chapter, chapter 2, describes our research on an experimental type of drug. This
drug influences protein production by targetting the blueprints (RNAs) for the
production of proteins. We show that the effects of such drugs are dependent on
the type and severity of the heart disease.
In the next study, described in chapter 3, we investigated how the type of
drugs studied in chapter 2 can be delivered to the heart. Because of blood flow,
injecting the drug into the heart directly will probably result in very quick washout
of the drug. To prevent this, we injected the drug into the muscle tissue of the
heart using a solution that forms a gel after injection. We show that this manner
of injection is safe and results in a slightly stronger local effect of the drug. However,
we cannot prove that delivering the drug in gel leads to improved cardiac
repair in injured hearts.
In order to develop novel drugs that are
based on RNA-targeting, it is essential to
know the RNA composition of cells within
a diseased heart. In the fourth chapter, we
studied the RNA composition of heart cells
from patients with a hereditary cardiac
disease. Our comprehensive dataset, linking
cell size and gene expression, will enable future
researchers to identify new RNAs that
can be targeted to improve heart function.