Single intracoronary injection of encapsulated antagomir-92a promotes angiogenesis and prevents adverse infarct remodeling.

Abstract

BACKGROUND:

Small and large preclinical animal models have shown that antagomir-92a-based therapy reduces early postischemic loss of function, but its effect on postinfarction remodeling is not known. In addition, the reported remote miR-92a inhibition in noncardiac organs prevents the translation of nonvectorized miR-targeted therapy to the clinical setting. We investigated whether a single intracoronary administration of antagomir-92a encapsulated in microspheres could prevent deleterious remodeling of myocardium 1 month after acute myocardial infarction

AUTHOR:

Should "acute" be added before "myocardial infarction" (since abbreviation is AMI)? Also check at first mention in main text (AMI) without adverse effects.

METHODS AND RESULTS:

In a percutaneous pig model of reperfused AMI, a single intracoronary administration of antagomir-92a encapsulated in specific microspheres (9 μm poly-d,-lactide-co-glycolide [PLGA]) inhibited miR-92a in a local, selective, and sustained manner (n=3 pigs euthanized 1, 3, and 10 days after treatment; 8×, 2×, and 5×-fold inhibition at 1, 3, and 10 days). Downregulation of miR-92a resulted in significant vessel growth (n=27 adult minipigs randomly allocated to blind receive encapsulated antagomir-92a, encapsulated placebo, or saline [n=8, 9, 9]; P=0.001), reduced regional wall-motion dysfunction (P=0.03), and prevented adverse remodeling in the infarct area 1 month after injury (P=0.03). Intracoronary injection of microspheres had no significant adverse effect in downstream myocardium in healthy pigs (n=2), and fluorescein isothiocyanate albumin-PLGA microspheres were not found in myocardium outside the left anterior descending coronary artery territory (n=4) or in other organs (n=2).

CONCLUSIONS:

Early single intracoronary administration of encapsulated antagomir-92a in an adult pig model of reperfused AMI prevents left ventricular remodeling with no local or distant adverse effects, emerging as a promising therapeutic approach to translate to patients who suffer a large AMI.

• Authors: Neus Bellera, Ignasi Barba, Antonio Rodriguez-Sinovas, Eulalia Ferret, Miguel Angel Asín, M Teresa Gonzalez-Alujas, Jordi Pérez-Rodon, Marielle Esteves, Carla Fonseca, Nuria Toran, Bruno Garcia Del Blanco, Amadeo Pérez, David Garcia-Dorado
• Journal: Journal of the American Heart Association (J Am Heart Assoc) Vol. 3 Issue 5 Pg. e000946 (Sep 19 2014) ISSN: 2047-9980 [Electronic] England
• PMID: 25240056 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Chemical References

• MicroRNAs
• Oligonucleotides

Topics

• Animals
• Disease Models, Animal
• Gene Expression Regulation
• Injections
• Male
• MicroRNAs (antagonists & inhibitors, genetics, metabolism)
• Microspheres
• Myocardial Contraction
• Myocardial Infarction (genetics, metabolism, pathology, physiopathology, therapy)
• Myocardial Reperfusion
• Neovascularization, Physiologic
• Oligonucleotides (administration & dosage, chemistry)
• Recovery of Function
• Swine
• Swine, Miniature
• Time Factors
• Ventricular Function, Left
• Ventricular Pressure
• Ventricular Remodeling