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In Vivo Nanovector Delivery of a Heart-specific MicroRNA-sponge
Published on: June 15, 2018
Cardiac-specific miRNA in cardiogenesis, heart function, and cardiac pathology (with focus on myocardial infarction)
Dimitry A Chistiakov1, Alexander N Orekhov2, Yuri V Bobryshev3
1Department of Molecular Genetic Diagnostics and Cell Biology, Division of Laboratory Medicine, Institute of Pediatrics, Research Center for Children's Health, 119991 Moscow, Russia.
Insights
Cardiac microRNAs (miRNAs) are key regulators of heart development and function. Altered levels in myocardial infarction (MI) suggest diagnostic potential and roles in cardiac repair and regeneration.
Area of Science:
- Cardiovascular Biology
- Molecular Cardiology
- Regenerative Medicine
Background:
- Cardiac microRNAs (miRNAs) like miR-1, miR-133a, miR-208a/b, and miR-499 are highly expressed in the heart.
- These miRNAs are crucial for cardiogenesis, regulating early lineage commitment and later differentiation into cardiomyocytes.
- They also control cardiac function, electrophysiology, and sarcomeric protein expression.
Purpose of the Study:
- To elucidate the multifaceted roles of cardiac-specific miRNAs in heart development, function, and disease.
- To explore the diagnostic potential of circulating cardiac miRNAs in acute myocardial infarction (MI).
- To assess the utility of cardiac miRNAs in cardiac regeneration strategies.
Main Methods:
- Review of existing literature on cardiac miRNA expression and function.
- Analysis of miRNA involvement in cardiogenesis and mature heart physiology.
- Examination of miRNA dysregulation in cardiac pathology, particularly MI.
- Evaluation of miRNA roles in stem cell therapy and cell reprogramming.
Main Results:
- miR-1 and miR-133a are vital for early cardiogenesis and cardiac automaticity.
- miR-208 and miR-499 regulate cardiomyocyte differentiation and sarcomeric protein expression.
- Cardiac miRNA expression is significantly altered in MI, correlating with adverse cardiac remodeling.
- Elevated circulating cardiac miRNAs in acute MI show promise as diagnostic biomarkers.
- Cardiac miRNAs enhance stem cell survival and promote reprogramming of non-cardiac cells into cardiomyocytes.
Conclusions:
- Cardiac miRNAs are essential regulators of heart development, function, and response to injury.
- Circulating cardiac miRNAs represent promising biomarkers for early acute MI detection.
- These miRNAs hold significant potential for advancing cardiac regenerative therapies.
Abstract:
Cardiac miRNAs (miR-1, miR133a, miR-208a/b, and miR-499) are abundantly expressed in the myocardium. They play a central role in cardiogenesis, heart function and pathology. While miR-1 and miR-133a predominantly control early stages of cardiogenesis supporting commitment of cardiac-specific muscle lineage from embryonic stem cells and mesodermal precursors, miR-208 and miR-499 are involved in the late cardiogenic stages mediating differentiation of cardioblasts to cardiomyocytes and fast/slow muscle fiber specification. In the heart, miR-1/133a control cardiac conductance and automaticity by regulating all phases of the cardiac action potential. miR-208/499 located in introns of the heavy chain myosin genes regulate expression of sarcomeric contractile proteins. In cardiac pathology including myocardial infarction (MI), expression of cardiac miRNAs is markedly altered that leads to deleterious effects associated with heart wounding, arrhythmia, increased apoptosis, fibrosis, hypertrophy, and tissue remodeling. In acute MI, circulating levels of cardiac miRNAs are significantly elevated making them to be a promising diagnostic marker for early diagnosis of acute MI. Great cardiospecific capacity of these miRNAs is very helpful for enhancing regenerative properties and survival of stem cell and cardiac progenitor transplants and for reprogramming of mature non-cardiac cells to cardiomyocytes.
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