Exosomes as a delivery tool of exercise-induced beneficial factors for the prevention and treatment of cardiovascular disease: a systematic review and meta-analysis

Abstract

Exercise-derived exosomes have been identified as novel players in mediating cell-to-cell communication in the beneficial effects of improving cardiovascular disease (CVD). This review aimed to systematically investigate exosomes as delivery tools for the benefits of exercise in the prevention and treatment of CVD and summarize these outcomes with an overview of their therapeutic implications. Among the 1417 articles obtained in nine database searches (PubMed, EBSCO, Embase, Web of Science, CENTRAL, Ovid, Science Direct, Scopus, and Wiley), 12 articles were included based on eligibility criteria. The results indicate that exercise increases the release of exosomes, increasing exosomal markers (TSG101, CD63, and CD81) and exosome-carried miRNAs (miR-125b-5p, miR-122-5p, miR-342-5p, miR-126, miR-130a, miR-138-5p, and miR-455). These miRNAs mainly regulate the expression of MAPK, NF-kB, VEGF, and Caspase to protect the cardiovascular system. Moreover, the outcome indicators of myocardial apoptosis and myocardial infarction volume are significantly reduced following exercise-induced exosome release, and angiogenesis, microvessel density and left ventricular ejection fraction are significantly increased, as well as alleviating myocardial fibrosis following exercise-induced exosome release. Collectively, these results further confirm that exercise-derived exosomes have a beneficial role in potentially preventing and treating CVD and support the use of exercise-derived exosomes in clinical settings.

Keywords: cardiovascular disease; exercise; exosomes; extracellular vesicles; meta-analysis.

FIGURE 1

Flowchart of the study selection process in the systematic review according to PRISMA guidelines.

FIGURE 2

Risk of bias results. Review authors’ judgments about each risk of bias item for each included study. +, low risk of bias; -, high risk of bias; ?, unclear risk of bias.

FIGURE 3

Contour-enhanced funnel plot of outcome indicators. Yellow dot, A total of seven articles provided relevant data on the myocardial apoptosis (n = 7); red dot, A total of four articles provided relevant data on the myocardial infarction volume (n = 4); green dot, A total of four articles provided relevant data on the angiogenesis (n = 4); purple dot, A total of two articles provided relevant data on the microvessel density (n = 2); blue dot, A total of two articles provided relevant data on the left ventricular ejection fraction (n = 2). , 1% < p < 5%; , 5% < p < 10%; , p > 10%; , Estimated θ_Ⅳ.

FIGURE 4

Forest plot of outcome indicators (A), Myocardial apoptosis; (B), Myocardial infarction volume; (C), Angiogenesis; (D), Microvessel density; (E), Left ventricular ejection fraction.

FIGURE 5

Exercise-induced release of exosome source, isolation method, characterization, exosome markers (proteins) and exosome-carried cargos.

FIGURE 6

Exercise induces multiple tissues to release exosomes, which mediate cardiovascular protection. The main effects of exercise on exosome source of release, which can derive from different organs (liver, brain, muscle, heart, and adipose tissue), cargo, and exercise-released exosome-carried miRNAs predicted actions. Exercise promotes cardiovascular health by mediating cell-to-cell communication and cross-talk between organs and tissues—exosomes are significant vehicles for miRNAs and proteins.