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Inhaled miR-133-loaded nanoparticles restore cardiac performance

ESC Congress News 2019 - Paris, France

In a Science Box session this morning, Doctor Daniele Catalucci (National Research Council-Institute of Genetic and Biomedical Research and Humanitas Research Hospital, Milan, Italy) will present results showing that a novel inhaled miR-133-loaded nanoparticle delivery approach can prevent cardiac dysfunction in an experimental model (Abstract 3072).

Basic Science
Basic Science - Cardiac Diseases - Heart Failure


Non-coding micro-RNAs (miRNAs), like miR-133, are implicated in cardiovascular diseases and their downregulation within the myocardium has been observed in cardiac pathologies.1 Restoring levels may repair myocardial damage but effective delivery of exogenous miR-133 has been elusive. Inspired by the way that inhaled ultrafine pollution particles reach the heart via the circulation, Dr. Catalucci and his team began working with inhaled non-toxic, biodegradable nanoparticles as a way of directly targeting cardiomyocytes. Providing protection against RNase degradation, the calcium-phosphate nanoparticles (CaPs) are negatively charged so as to be attracted to polarised cells, such as cardiomyocytes.2 Once at the cells, the nanoparticles are internalised and release miR-133. This direct, non-invasive approach bypasses hepatic, renal and gastric degradation, meaning that relatively low doses of miR-133 would be required.

Dr. Catalucci and his team used the transaortic constriction (TAC) to induce ventricular pressure overload and heart failure in mice. TAC and non-TAC groups received either saline, CaP-miR-133, miR-133 alone or unloaded CaPs alone, delivered by intratracheal nebulisation on alternate days for four consecutive weeks. Echocardiographic analyses were performed at two and four weeks after surgery.

Notably, CaP-miR-133 led to reversal of heart failure progression, with preservation of left ventricular internal diameter, ejection fraction and fractional shortening, together with a reduction in myocardial fibrosis.

The improvement in cardiac function was associated with restoration of cardiomyocyte levels of miR-133.CaP-miR-133 administration was not associated with any major changes in immunological status. No beneficial effects were seen with miR-133 alone or unloaded CaPs alone.
“This proof of concept has never been shown before for miRNAs and inhalation,” says Dr. Catalucci. “This important work represents a European collaboration between academia and industry (CUPIDO project, www.cupidoproject.eu) and we are now in the process of scaling up production ready for evaluation in large-animal models, with the hope it might lead to a first-in-class investigation in humans.”

 

Don’t miss today!
Myocardial delivery of therapeutic miR-133 via inhalable nanoparticles prevents the pathologic development in a model of ventricular pressure overload
Heart failure: from bench to bed
08:30 – 10:00; Science Box 1 – Poster Area

 

 

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References

1. Di Mauro V, et al. Noncoding RNA Res 2018;3:12–19.

2. Di Mauro V, et al. Nanomedicine (Lond) 2016;11:891–906.

Notes to editor

About the European Society of Cardiology

The European Society of Cardiology brings together healthcare professionals from more than 150 countries, working to advance cardiovascular medicine and help people lead longer, healthier lives.

About ESC Congress 2019

ESC Congress is the world’s largest and most influential cardiovascular event contributing to global awareness of the latest clinical trials and breakthrough discoveries. ESC Congress 2019 takes place 31 August to 4 September at the Paris Expo Porte de Versailles, Paris - France. Explore the scientific programme