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Micro-RNAs in the heart: small molecules with major impact

MicroRNAs are finding their way into the heart

Heart Failure (HF)


Dr Abdellatif (USA) reported on Mir199a in cardiac hypertrophy. She showed that Mir-199a is rapidly decreased after ischemia and Hif1α is a direct target of Mir199a. Mir-199a overexpression in cardiomyocytes inhibited hypoxia induced Hif1α and p53 and blocked apoptosis. Interestingly, knockdown of Mir-199a in normal cardiomyocytes induced the expression of Hif1α, mimicking preconditioning. Therefore, Mir-199a antisense reagents could be used to reduce ischemia induced organ damage.  

Dr Domain (USA) presented cardiac progenitor cells. Making use of genetically modified ES cells he reported the existence of an Isl+/Nkx2.5+ progenitor with high myogenic capacity. Allowing ES cells to differentiate making embyoid bodies, they found the same microRNA profile as was described for the heart, showing that EB differentiation mimicked heart development.

Dr Tum (Germany) talked about mir-21. Mir-21 was picked up in a study by the group of Dr de Windt, who analyzed a cardiomyocyte specific Dicer deficient mouse. While all cardiomyocyte specific mirs are inhibited, Mir-21 as well as mir-199a, were still expressed. Dr Tum identified the cardiac fibroblast as the Mir-21 target cell in the heart. In failing hearts, Mir-21 expression is increased in cardiac fibroblasts, leading to the knockdown of Sprouty-1 and repression of apoptosis. Using antagomirs, Mir-21 expression was knocked down in vivo, blocking fibrosis when administered 1 day after TAC. Interestingly, when mir-21 was knocked down 3 weeks after TAC, the ejection fraction improved making it a perfect candidate to reduce fibroses.

Finally, Dr Condorelli (Italy) gave a beautiful historic overview of microRNAs, making it clear that microRNAs just entered the field of cardiology. He also presented data describing the function of mir-133. The target for mir-133 causing this effect is still not clear, but the results point towards RhoA, CDC25 or NEFL-A, especially NEFL-A, since it is being induced after TAC. Mir-133 was shown to affect cardiomyocyte size in vitro. Interestingly, knockdown of Mir-133 in vivo, using antagomirs, induced hypertrophy, demonstrating an important role in the development of heart failure.

Conclusion:

We can no longer ignore the important regulatory function of microRNAs in cardiac pathologies. Although it is still in its infancy, the presented preclinical data, together with microRNA expression levels in vivo, is very promising. However, much more work needs to be done before it can be translated into new therapies.

References


375-376-377-378

SessionTitle:

Micro-RNAs in the heart: small molecules with major impact

Notes to editor


This congress report accompanies a presentation given at the ESC Congress 2008. Written by the author himself/herself, this report does not necessarily reflect the opinion of the European Society of Cardiology.

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.