A new study analyses how mRNA changes during the progression of atherosclerosis

Researchers from the Bellvitge Biomedical Research Institute (IDIBELL) and the Germans Trias i Pujol Research Institute (IGTP) have studied variations in mRNA length during the progression of atherosclerosis in a mouse model. The results, published in the journal Biomedicines, could help identify new biomarkers and potential therapeutic targets.

Atherosclerosis is a disease in which arteries narrow and become more rigid due to the accumulation of fat and other substances on their walls. This process can lead to serious cardiovascular problems, such as heart attacks or strokes. Although it is known that factors such as high cholesterol and inflammation play a key role in its progression, many molecular aspects remain to be understood.

The role of miRNA and mRNA in gene regulation

The recent Nobel Prize in Medicine awarded to Victor Ambros and Gary Ruvkun for their discovery of microRNAs (miRNAs) has brought global attention to these small regulators of mRNA stability and function. Research into miRNA-mRNA interactions initially suggested a passive role for the latter, but recent studies point to a more complex relationship, in which mRNAs can modify their own accessibility to miRNAs by adjusting the length of their untranslated regions (UTRs), a process that is often altered in certain diseases.

The Research in Kidney Affecting Diseases Group (REMAR) at IGTP has long been studying the role of molecular alterations in various pathologies, particularly in cardiovascular complications associated with kidney disease and atherosclerosis. For example, they have characterised the transcriptome (mRNA, lncRNA, and miRNA) of aortas in an atherosclerosis mouse model, both during disease progression and after regression following treatment. And they have also identified miR-125b as a specific biomarker for the disease.

How does mRNA change in atherosclerosis?

In a new study published in the journal Biomedicines, researcher Estanis Navarro from REMAR-IGTP and two researchers from IDIBELL, Miguel Hueso and Adrián Mallén, have analysed global changes in mRNA length in a murine model of atherosclerosis progression. They observed variations in the 5'UTR, 3'UTR, and coding regions of mRNAs, which become shorter as atherosclerosis progresses.

Additionally, the authors suggest that alternative splicing reprogramming and transcript isoform switching -mechanisms that generate different versions of the same gene- may play a role in generating diversity and variability in mRNA sequences related to the disease.

Towards a better understanding of the disease

Having confirmed that significant changes occur in the length of transcripts with altered expression during the progression of atherosclerosis, the researchers have begun a more detailed characterisation of the affected mRNAs, as well as the mechanisms and regulatory networks involved in generating these variants. In particular, they are focusing on how splicing-regulating factors may influence this process.

Although this study is based on an animal model and takes a basic research approach, Navarro is hopeful about the implications of these findings: "We are aware of the potential of this work to describe new biomarkers of disease progression and to identify novel gene products or regulatory networks that could be targeted for future treatments".