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Published on: June 11, 2020
Non-Coding RNAs in the Therapeutic Landscape of Pathological Cardiac Hypertrophy
Joana Silva1,2, Paula A da Costa Martins1,3
1Department of Cardiology, CARIM School for Cardiovascular Diseases, Faculty of Health, Medicine and Life Sciences, Maastricht University, 6229 ER Maastricht, The Netherlands.
Insights
Non-coding RNAs (ncRNAs) show therapeutic potential for treating pathological cardiac hypertrophy, a major contributor to heart failure mortality. Oligonucleotide therapies targeting these ncRNAs are advancing, with some already in clinical trials.
Area of Science:
- Cardiovascular Research
- Molecular Medicine
- RNA Therapeutics
Background:
- Cardiovascular diseases, particularly heart failure, remain a significant global health burden with limited long-term survival rates.
- Pathological cardiac hypertrophy is a primary driver of morbidity and mortality in heart failure, lacking effective treatments.
- Non-coding RNAs (ncRNAs) are emerging as critical regulators of cardiac hypertrophy pathways, presenting novel therapeutic targets.
Purpose of the Study:
- To review the molecular mechanisms of cardiac hypertrophy.
- To explore the role of ncRNAs in cardiac hypertrophy.
- To discuss the therapeutic potential of oligonucleotide-based therapies targeting ncRNAs for heart failure.
Main Methods:
- Literature review of preclinical and clinical studies.
- Analysis of molecular mechanisms involving ncRNAs in cardiac hypertrophy.
- Evaluation of oligonucleotide delivery strategies and therapeutic approaches.
Main Results:
- ncRNAs play a significant role in regulating the signaling pathways of cardiac hypertrophy.
- Preclinical studies in animal models demonstrate successful amelioration of cardiac hypertrophy using ncRNA-targeting drugs.
- An antisense oligonucleotide therapy for heart failure has progressed to clinical trials.
Conclusions:
- ncRNA-targeting therapies represent a promising new avenue for treating pathological cardiac hypertrophy and heart failure.
- Advances in oligonucleotide drug delivery are crucial for overcoming current challenges and realizing the clinical potential of these therapies.
- ncRNA-based treatments for cardiac hypertrophy are becoming an increasingly attainable reality in clinical practice.
Abstract:
Cardiovascular diseases are a major health problem, and long-term survival for people diagnosed with heart failure is, still, unrealistic. Pathological cardiac hypertrophy largely contributes to morbidity and mortality, as effective therapeutic approaches are lacking. Non-coding RNAs (ncRNAs) arise as active regulators of the signaling pathways and mechanisms that govern this pathology, and their therapeutic potential has received great attention in the last decades. Preclinical studies in large animal models have been successful in ameliorating cardiac hypertrophy, and an antisense drug for the treatment of heart failure has, already, entered clinical trials. In this review, we provide an overview of the molecular mechanisms underlying cardiac hypertrophy, the involvement of ncRNAs, and the current therapeutic landscape of oligonucleotides targeting these regulators. Strategies to improve the delivery of such therapeutics and overcome the actual challenges are, also, defined and discussed. With the fast advance in the improvement of oligonucleotide drug delivery, the inclusion of ncRNAs-targeting therapies for cardiac hypertrophy seems, increasingly, a closer reality.
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