MicroRNAs as Biomarkers of Systemic Changes in Response to Endurance Exercise-A Comprehensive Review

Abstract

Endurance sports have an unarguably beneficial influence on cardiovascular health and general fitness. Regular physical activity is considered one of the most powerful tools in the prevention of cardiovascular disease. MicroRNAs are small particles that regulate the post-transcription gene expression. Previous studies have shown that miRNAs might be promising biomarkers of the systemic changes in response to exercise, before they can be detected by standard imaging or laboratory methods. In this review, we focused on four important physiological processes involved in adaptive changes to various endurance exercises (namely, cardiac hypertrophy, cardiac myocyte damage, fibrosis, and inflammation). Moreover, we discussed miRNAs' correlation with cardiopulmonary fitness parameter (VO_2max). After a detailed literature search, we found that miR-1, miR-133, miR-21, and miR-155 are crucial in adaptive response to exercise.

Keywords: adaptive changes; cardiac fibrosis; cardiac hypertrophy; endurance sport; microRNA.

Figure 1

The potential role of microRNAs in cardiac remodeling. (a) MicroRNAs associated with ibeneficial response to endurance exercise. (b) MicroRNAs associated with pro-inflammatory, pro-fibrotic and pro-hypertrophic processes in cardiac remodeling. miR, microRNA.

Figure 2

Regulation of cardiac remodeling by microRNAs and the functions of their target mRNAs. MAPK/ERK pathway plays a crucial impact on signal transduction for myosin growth. PI3K/AKT signaling pathway regulates cell proliferation, metabolism, survival, and angiogenesis and controls the development and transformation of left ventricular hypertrophy. The ERK signaling pathway, a member of the MAPK family, comprises a cascade of a series of successively acting kinases. (a) The role of miR-21 in cardiac remodeling. Regulation of ERK is mediated by miR-21 via inhibiting PTEN and SMAD7 gene expression. (b) The role of miR-133 in cardiac remodeling. MicroRNA-133 plays a role in determining cardiomyocyte hypertrophy by targeting PP2AC. Abbreviations: miR, microRNA; STAT3, signal transducer and activator of transcription 3; NF-κB, nuclear factor-κB; PTEN, phosphatase and tensin homolog; ERK, extracellular signal-regulated kinase; MAPK, mitogen-activated protein kinase; PP2AC, protein phosphatase 2A; Raf-1, Raf-1 proto-oncogene, serine/threonine kinase.