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MICARUS Report Summary

Project ID: 615708
Funded under: FP7-IDEAS-ERC
Country: Netherlands

Mid-Term Report Summary - MICARUS (MicroRNA function in cardiac and metabolic disease)

Cardiovascular disease remains the primary cause of morbidity and mortality worldwide. Despite the therapeutic benefits of numerous treatment options, including statins, angiotensin-converting enzyme (ACE) inhibitors, beta blockers and other drugs, the prevalence of cardiovascular disease continues to increase, underscoring the need for new therapeutic strategies. In recent years, prominent roles for microRNAs (miRNAs) have been uncovered in a variety of cardiovascular disorders. MiRNAs are short, single stranded RNAs that regulate gene expression by suppressing multiple, often related, mRNAs. Thus, the regulation of a single miRNA can have a profound impact on cellular phenotypes.
Our studies have focused on the cardiac specific miRNA, miR-208. We showed that, in the setting of heart disease, genetic deletion as well as therapeutic inhibition of miR-208 resulted in reduced cardiac remodeling (less cardiomyocyte hypertrophy and fibrosis) and improved survival.
Since microRNAs function through the regulation of several downstream genes, the cardioprotective effect of miR-208a inhibition allowed for the identification of new factors relevant for cardiac disease.
So far our studies have shown that Zeb2 and Sox9, downstream of miR-208a, are 2 newly identified cardioprotective factors that are expressed within the cardiomyocyte. Increased levels of both Sox9 and Zeb2 seem to introduce a beneficial effect for the cardiomyocyte, indicating the further therapeutic potential of using antimiR-208a in the setting of heart disease.
The obvious relevance of miR-208a and how this research can lead to the discovery of new relevant gene targets has triggered a lot of excitement to identify novel microRNAs relevant for additional forms of heart disease. Our lab is currently investigating the contribution of new microRNA targets in the setting of cardiometabolic disease.

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