Heart failure is a serious clinical disorder that represents the primary cause of hospitalization and death in Europe and the United States. Numerous cardiovascular diseases, including hypertension, coronary artery disease, myocardial infarction (MI) and genetic forms of cardiomyopathies result in heart failure, which is associated with pathological remodeling of the myocardium, pump failure and sudden death. While classical pharmacological treatment strategies (e.g. β-blockers and ACE-inhibitors) have shown effectiveness in prolonging survival of heart failure patients, the prognosis of affected individuals remains poor and there is a dire need for new paradigms and therapeutic approaches for treatment of this devastating disease. 

Rarely has such a unique opportunity existed to exploit an entirely new biology of heart disease, as has been provided by the recent discovery of a family of regulatory RNAs, known as microRNAs (microRNAs). MicroRNAs are small, noncoding RNAs (20-23 nucleotides) that negatively regulate gene expression at the post-transcriptional level by base-pairing with complementary sequences in the 3' untranslated regions (UTRs) of protein-coding transcripts (Fig. 1). There are estimates that over 1000 microRNAs are encoded in the human genome.4 Individual mRNAs are commonly targeted by multiple microRNAs, allowing for enormous regulatory potential. An especially powerful facet of microRNA biology is the ability of individual microRNAs to coordinately regulate target mRNAs encoding proteins with related functions (e.g. cell growth, contractility, etc), in contrast to classical drugs, which act on specific cellular targets.

Our Leducq network includes experts from all areas needed to bridge basic microRNA research to (pre-)clinical application. The members of this Leducq proposal believe that harnessing the potential of microRNA-control of gene expression represents a unique opportunity to develop entirely new treatment paradigms for cardiovascular disease. 

microRNA-Leducq website