Atherosclerosis is a disease in which the arteries narrow and become stiffer due to the accumulation of fat and other substances in their walls. This process can lead to serious cardiovascular problems, such as heart attacks or strokes. Although factors such as high cholesterol and inflammation are known to play an important role in its progression, there are still many molecular aspects to be understood.
The role of miRNAs and mRNAs in gene regulation
The recent Nobel Prize in Medicine awarded to Victor Ambros and Gary Ruvkun for their discovery of microRNAs (miRNAs) has put the global spotlight on these small regulators of the stability and function of messenger RNAs (mRNAs). The research that has been done to study the interaction between miRNA and mRNA proposed a passive role for the latter, but more recent work points to a more complex relationship, where mRNAs can modify their own accessibility to miRNAs by adjusting the length of their untranslated regions (UTRs) through a process that is often altered in some diseases.
The team behind this study has been studying the role of molecular alterations in various pathologies, especially in cardiovascular complications associated with kidney disease and atherosclerosis. They have described, for example, the transcriptome (mRNA, lncRNA and miRNA) of the aortas of a mouse model of atherosclerosis, both in its progression and in its regression after treatment. And they have also identified miR-125b as a disease-specific biomarker.
How are mRNAs modified in atherosclerosis?
In a new study published in the journal Biomedicines, researcher Estanis Navarro, from REMAR-IGTP, and two researchers from IDIBELL’s Nephrology and renal transplantation group, Miguel Hueso and Adrián Mallén, have analysed global changes in mRNA length in a mouse model of atherosclerosis progression. They have observed variations in the 5’UTR, 3’UTR and mRNA coding regions, which are reduced during the progression of atherosclerosis.
In addition, the authors propose that the reprogramming of alternative splicing and the change of transcript isoforms – mechanisms that generate different versions of the same gene – could play a role in the generation of diversity and variability in disease-related mRNA sequences.
Towards a better understanding of the disease
Having confirmed that significant changes in the length of transcripts with altered expression occur during the progression of atherosclerosis, the researchers have initiated a more detailed characterization of the affected mRNAs, as well as the mechanisms and regulatory networks that have contributed to generating these variants. In particular, they have focused on how the factors that regulate splicing could influence this process.
Although the work is based on an animal model and has a basic approach, Navarro is hopeful about the implications of these discoveries: “We are aware of the potential of this work to describe new biomarkers of disease progression and to identify new gene products or regulatory networks that may be targeted by future treatments.”
The Bellvitge Biomedical Research Institute (IDIBELL) is a biomedical research center created in 2004. It is participated by the Bellvitge University Hospital and the Viladecans Hospital of the Catalan Institute of Health, the Catalan Institute of Oncology, the University of Barcelona and the City Council of L’Hospitalet de Llobregat.
IDIBELL is a member of the Campus of International Excellence of the University of Barcelona HUBc and is part of the CERCA institution of the Generalitat de Catalunya. In 2009 it became one of the first five Spanish research centers accredited as a health research institute by the Carlos III Health Institute. In addition, it is part of the “HR Excellence in Research” program of the European Union and is a member of EATRIS and REGIC. Since 2018, IDIBELL has been an Accredited Center of the AECC Scientific Foundation (FCAECC).