Evaluation of the cardioprotective potential of extracellular vesicles - a systematic review and meta-analysis

Abstract

Cardiovascular diseases are the main cause of death worldwide, demanding new treatments and interventions. Recently, extracellular vesicles (EVs) came in focus as important carriers of protective molecules such as miRNAs and proteins which might contribute to e.g. improved cardiac function after myocardial infarction. EVs can be secreted from almost every cell type in the human body and can be transferred via the bloodstream in almost every compartment. To provide an all-encompassing overview of studies investigating these beneficial properties of EVs we performed a systematic review/meta-analysis of studies investigating the cardioprotective characteristics of EVs. Forty-three studies were investigated and catalogued according to the EV source. We provide an in-depth analysis of the purification method, size of the EVs, the conducted experiments to investigate the beneficial properties of EVs as well as the major effector molecule encapsulated in EVs mediating protection. This study provides evidence that EVs from different cell types and body fluids provide cardioprotection in different in vivo and in vitro studies. A meta-analysis was performed to estimate the underlying effect size. In conclusion, we demonstrated that EVs from different sources might serve as a promising tool for treating cardiovascular diseases in the future.

Figure 1

Flow chart of study selection.

Figure 2

Summary of in EVs encapsulated molecules mediating cardio protective or detrimental impact. Molecules are ordered by origin. Thumbs up indicate a general positive impact of EVs derived from the particular source. Thumps down indicate a detrimental impact. Effector molecules surrounded by solid lines are specific for a positive impact whereas a dashed line stands for molecules with a negative impact. Proteins are surrounded by a circle, miRNAs by a rectangle.

Figure 3

Forest plots showing the results of meta-analysis of the effect of formation of new capillaries upon a treatment with EVs. Data are expressed as standard mean difference with 95% confidence interval.

Figure 4

Forest plots showing the results of meta-analysis of the effect of protecting cardiomyocytes from hypoxia-reoxygenation injury after a treatment with EVs. Data are expressed as mean difference with 95% confidence interval.