The doctoral dissertation in the field of Cardiovascular Genomics will be examined at the Faculty of Health Sciences at Kuopio campus. The public examination will be streamed online.
What is the topic of your doctoral research? Why is it important to study the topic?
Atherosclerosis is a major contributor to global disability and mortality, imposing significant medical burdens on nations. This chronic inflammatory disease affects blood vessel walls, where plaques develop. Rupture of plaques can trigger blood clot formation and lead to life-threatening cardiovascular events. Various cell types in the vessel wall that contribute to the development of these plaques. Endothelial cells (ECs), which line the inside of the blood vessels, macrophages (a type of immune cell, abbreviated as Mɸs), and smooth muscle cells (SMCs) are all key players. Their actions in the disease are influenced by various genetic factors, including non-coding RNAs (ncRNAs) —molecules that help regulate what happens inside cells but do not produce proteins. These non-coding RNAs include types called long non-coding RNAs and microRNAs, which have specific effects depending on the cell type. However, the precise roles of these cells and how they interact at the molecular level are still not fully understood, partly because it’s challenging to distinguish the unique RNA patterns in each cell type. Understanding these interactions better could lead to more effective treatments for atherosclerosis.
What are the key findings or observations of your doctoral research?
This thesis uses next-generation sequencing techniques to investigate how microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) regulate key processes in atherosclerosis-related cell types and under various stimuli.
The first study examined gene expression profiles in endothelial cells (ECs), smooth muscle cells (SMCs), and macrophages (Mɸs) exposed to atherosclerosis-promoting stimuli, identifying shared and cell-specific miRNA patterns. Notably, miR-100-5p was found highly expressed in all cell types but played different roles in each. The second study focused on endothelial cells and the changes occurring in low oxygen environment (also known as hypoxia), revealing the regulation of around 1800 long non-coding RNAs (lncRNAs) and their impact on controlling genes that make the cells either grow new vessels or survive under stress, key processes in atherosclerotic lesion development. Finally, the third study delved into the specific functions of lncRNAs in different cellular compartments of ECs in low oxygen environment identifying lncRNAs implicated in inflammation and cell growth, suggesting potential therapeutic targets. These findings enhance our understanding of ncRNA contributions to cardiovascular diseases, paving the way for targeted therapies against atherosclerosis.
How can the results of your doctoral research be utilised in practice?
These findings underscore the significance of ncRNAs in cardiovascular diseases and provide a better understanding of the roles of miRNAs and ncRNAs in atherosclerosis-related cell types. Ultimately, these findings advance our understanding of disease development.
What are the key research methods and materials used in your doctoral research?
In this thesis, endothelial cells (ECs), smooth muscle cells (SMCs), and macrophages (Mɸs) were cultured in-vitro and exposed to hypoxia (low oxygen environment) and/or OxPAPC (oxidized 1-palmitoyl-2-arachidonoyl-sn-glycerol-3-phosphocholine), two pro-atherogenic stimuli that mimic thickening of the aorta vessel wall and high cholesterol, respectively.
Several advanced next-generation sequencing (NGS) techniques ranging from transcription factors binding, nascent transcription and mature RNA processing were integrated to discover and define the constitutive role of non-coding RNAs (ncRNAs).
Additionally, a diverse array of molecular biology techniques was utilized to manipulate the levels of identified ncRNAs, studying their functional significance and their impact on gene expression and cellular phenotypes associated with atherosclerosis progression.
The integration of these methods and materials provided insights into how ncRNAs regulate key pathways in atherosclerosis advancing our understanding of cardiovascular disease mechanisms.
The doctoral dissertation of Pierre Moreau, MSc, entitled Exploring the non-coding RNA landscape in atherosclerosis: Cellular and stimulus specific profiling of key regulatory elements will be examined at the Faculty of Health Sciences. The Opponent in the public examination will be Professor Lars Mägdefessel of the Technical University of Munich and Karolinska Institute, and the Custos will be Professor Minna Kaikkonen-Määttä of the University of Eastern Finland.
For further information, please contact:
Pierre Moreau, MSc, pierre.moreau@uef.fi
