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Updated: Mar 14, 2026
In Vivo Nanovector Delivery of a Heart-specific MicroRNA-sponge
Published on: June 15, 2018
Preclinical Development of a MicroRNA-Based Therapy for Elderly Patients With Myocardial Infarction
Shashi Kumar Gupta1, Ariana Foinquinos1, Sabrina Thum1
1Institute of Molecular and Translational Therapeutic Strategies, Hannover Medical School, Hannover, Germany.
Background:
Aging populations show higher incidences of myocardial infarction (MI) and heart failure (HF). Cardiac remodeling post-MI leads to progressive impaired cardiac function caused by a disarray of several processes including derailed autophagy. Microribonucleic acids (miRNAs) are known to be key players in cardiovascular disease but their involvement in cardiac autophagy and aging is not well understood.
Objectives:
This study sought to identify new miRNA candidates that regulate cardiac autophagy and aging.
Methods:
We exploited a high-throughput, fluorescence-activated cell sorting-based green fluorescent protein-LC3 detection method to measure the autophagic flux in cardiomyocytes after transfection of a precursor miRNA library consisting of 380 miRNAs. This was followed by a series of molecular and in vivo studies.
Results:
Together with additional expression screenings, we identified miR-22 as an abundant and strong inhibitor of the cardiac autophagy process. Cardiac miR-22 expression levels increased during aging of mice as well as in aging neonatal cardiomyocytes in vitro by a P53-dependent mechanism. Inhibition of miR-22 in aging cardiomyocytes in vitro activated autophagy and inhibited cellular hypertrophy. Pharmacological inhibition of miR-22 post-MI in older mice activated cardiac autophagy, prevented post-infarction remodeling, and improved cardiac function compared with control subjects. Interestingly, similar effects were less pronounced in younger mice with significantly lower cardiac miR-22 expression levels. In addition, circulating levels of miR-22 in 154 patients with systolic HF were highly associated with early mortality.
Conclusions:
We concluded that miR-22 is an important regulator of cardiac autophagy and a potential therapeutic target, especially in the older myocardium. Finally, circulating miR-22 provides prognostic information for HF patients, highlighting miR-22 as a promising therapeutic and biomarker candidate for cardiovascular disorders.
Insights
MicroRNAs, specifically miR-22, are key regulators of cardiac autophagy in aging hearts. Inhibiting miR-22 improves heart function post-myocardial infarction and shows prognostic value in heart failure patients.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Aging Research
Background:
- Aging populations face increased risks of myocardial infarction (MI) and heart failure (HF).
- Cardiac remodeling post-MI impairs heart function, partly due to dysregulated autophagy.
- The role of microRNAs (miRNAs) in cardiac autophagy and aging remains unclear.
Purpose of the Study:
- To identify novel miRNA candidates regulating cardiac autophagy and aging.
- To investigate the specific role of identified miRNAs in cardiovascular health during aging.
Main Methods:
- Utilized a high-throughput, fluorescence-activated cell sorting-based method to measure autophagic flux in cardiomyocytes.
- Screened a library of 380 precursor miRNAs to identify regulators of cardiac autophagy.
- Conducted molecular and in vivo studies, including experiments in aging mice.
Main Results:
- Identified miR-22 as a potent inhibitor of cardiac autophagy, with levels increasing with age via a P53-dependent mechanism.
- Inhibition of miR-22 in aging cardiomyocytes reduced hypertrophy and activated autophagy.
- Pharmacological inhibition of miR-22 post-MI in older mice improved cardiac function and prevented remodeling.
- Circulating miR-22 levels in heart failure patients correlated with mortality risk.
Conclusions:
- miR-22 is a critical regulator of cardiac autophagy and a potential therapeutic target, particularly in older individuals.
- Circulating miR-22 serves as a prognostic biomarker for heart failure patients.
- miR-22 represents a promising candidate for therapeutic intervention and diagnostics in cardiovascular disorders.
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