miR-208a in Cardiac Hypertrophy and Remodeling

Abstract

Various stresses, including pressure overload and myocardial stretch, can trigger cardiac remodeling and result in heart diseases. The disorders are associated with high risk of morbidity and mortality and are among the major health problems in the world. MicroRNAs, a class of ~22nt-long small non-coding RNAs, have been found to participate in regulating heart development and function. One of them, miR-208a, a cardiac-specific microRNA, plays key role(s) in modulating gene expression in the heart, and is involved in a broad array of processes in cardiac pathogenesis. Genetic deletion or pharmacological inhibition of miR-208a in rodents attenuated stress-induced cardiac hypertrophy and remodeling. Transgenic expression of miR-208a in the heart was sufficient to cause hypertrophic growth of cardiomyocytes. miR-208a is also a key regulator of cardiac conduction system, either deletion or transgenic expression of miR-208a disturbed heart electrophysiology and could induce arrhythmias. In addition, miR-208a appeared to assist in regulating the expression of fast- and slow-twitch myofiber genes in the heart. Notably, this heart-specific miRNA could also modulate the “endocrine” function of cardiac muscle and govern the systemic energy homeostasis in the whole body. Despite of the critical roles, the underlying regulatory networks involving miR-208a are still elusive. Here, we summarize the progress made in understanding the function and mechanisms of this important miRNA in the heart, and propose several topics to be resolved as well as the hypothetical answers. We speculate that miR-208a may play diverse and even opposite roles by being involved in distinct molecular networks depending on the contexts. A deeper understanding of the precise mechanisms of its action under the conditions of cardiac homeostasis and diseases is needed. The clinical implications of miR-208a are also discussed.

Circulating MicroRNAs and myocardial involvement severity in chronic Chagas cardiomyopathy

“…observed that patients with CCM had a significantly lower relative expression of miR-208a, measured in human myocardial samples, than healthy controls ( Ferreira et al., 2014 ). MiR-208a represents an essential regulator of several pathways involved in cardiac fibrosis and hypertrophy, being also associated with the development of conduction abnormalities and arrhythmias ( Wang et al., 2014 ; Huang et al., 2021 ). Although the role of this microRNA in CD is not clear, published evidence suggests that TGF-β may activate miR-208a to regulate genes related to hypertrophy, as TGF-β neutralizing antibody therapy attenuated miR-208a induced expression in myocytes ( Wang et al., 2013 ).…”

Extracellular vesicle-derived miRNAs improve stem cell-based therapeutic approaches in muscle wasting conditions

“…Similarly, miR-208a was among the most abundant circulating EV-derived miRNAs detected in both models. Albeit considered a specific cardiac miRNA, miR-208a is also a known regulator of myostatin , together with miR-208b and miR-499 ( 49 , 50 ), implying a potential role in driving skeletal muscle hypertrophy that thus far remained unexplored. This work proposes miR-208a as an additional modulator of myogenic commitment of progenitor cells.…”

Novel miRNA Biomarkers for Patients With Duchenne Muscular Dystrophy

“…Except for miR-206, the other six myomiRs, miR-1, miR-133a, miR-133b, miR-208a, miR-208b, and miR-499, can be expressed in cardiac muscles. Moreover, multiple studies have demonstrated that these myomiRs are involved in the development of different types of heart diseases, including dilated cardiomyopathy ( 33 ), coronary artery disease ( 34 ), cardiac hypertrophy ( 35 , 36 ), and myocardial fibrosis ( 37 , 38 ). Although miR-208a and miR-208b were not remarkably higher in the sera of cardiac involvement patients, we believe this may suggest that miR-1, miR-133a, miR-133b, and miR-499 are more sensitive to cardiac involvement.…”