MicroRNAs in heart and circulation during physical exercise

Lijun Wng,Yicheng Lv,Guoping Li,Junjie Xio*

aCardiac Regeneration and Ageing Lab,Institute of Cardiovascular Sciences,School of Life Science,Shanghai University,Shanghai 200444,China

bCardiovascular Division of the Massachusetts General Hospital and Harvard Medical School,Boston,MA 02215,USA

Abstract Exercise training is beneficial to the cardiovascular system.MicroRNAs(miRNAs,miRs)are a class of conserved non-coding RNAs and play a wide-ranging role in the regulation of eukaryotic gene expression.Exercise training alters the expression levels of large amounts of miRNAs in the heart.In addition,circulating miRNAs appear to be regulated by exercise training.In this review,we will summarize recent advances in the regulation of miRNAs during physical exercise intervention in various cardiovascular diseases,including pathologic cardiac hypertrophy,myocardial fibrosis,ischemia-reperfusion injury,myocardial infarction,and heart failure.The regulatory role of circulating miRNAs after exercise training was also reviewed.In conclusion,miRNAs might be a valuable target for treatment of cardiovascular diseases and have great potential as biomarkers for assessment of physical performance.

Keywords:Cardiovascular diseases;Circulating microRNAs;Exercise;MicroRNAs

Fig.1.Cardiac adaptations in response to exercise.The adaptations of the heart to exercise include changes in morphology(physiological hypertrophy),structure(angiogenesis),and function(improved vascular endothelial function and increased number of cardiomyocytes).AC=adenylyl cyclase;AKT=serine/threonine kinase;cAMP=cyclic adenosine monophosphate;C/EBPβ =CCAAT/enhancer binding protein β;CITED4=Cbp/p300 interacting transactivator with Glu/Asp rich carboxy-terminal domain 4;eNOS=endothelial nitric oxide synthase;GPCR=G protein-coupled receptor;NO=nitric oxide;PKA=cAMP-dependent protein kinase A;PI3K=phosphoinositide-3-kinase;RTK=receptor tyrosine kinase;VEGF=vascular endothelial growth factor;VEGFR=vascular endothelial growth factor receptor.

Fig.2.Exercise-regulated microRNAs that benefit the heart.MicroRNAs mediate the protective effects of exercise in cardiovascular diseases including myocardial fibrosis,ischemia-reperfusion injury,myocardial infarction,and heart failure.

Table 1 Summary of well-studied miRNAs involved in exercise protecting against cardiovascular diseases.

Fig.3.MicroRNAs that mediate exercise-induced cardiac physiological hypertrophy.

Table 2 Summary of the c-miRNAs in response to exercise.