Exercise-induced circulating extracellular vesicles protect against cardiac ischemia–reperfusion injury

Bei, Yihua; Xu, Tianzhao; Lv, Dongchao; Yu, Pujiao; Xu, Jiahong; Lin, Chen; Das, Avash; Tigges, John; Toxavidis, Vassilios; Ghiran, Ionita; Shah, Ravi; Li, Yongqin; Zhang, Yuhui; Das, Saumya; Xiao, Junjie

doi:10.1007/s00395-017-0628-z

Cited by 149 publications

(191 citation statements)

References 50 publications

Supporting

Mentioning

158

Contrasting

Unclassified

Order By: Relevance

“…EVs, and in particular their composite cargos, have been consistently demonstrated to contribute to the development of cardiovascular diseases 39 . However, the therapeutic delivery of stem cell-and serum-derived EVs have been proposed as cell-free approaches for cardioprotection in models of cardiac ischemic injury 8,20 . We have recently demonstrated that the sera of healthy donors could contain pro-angiogenic EVs, which principally express endothelial and platelet markers.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

miR-130a and Tgfβ Content in Extracellular Vesicles Derived from the Serum of Subjects at High Cardiovascular Risk Predicts their In-Vivo Angiogenic Potential

Cavallari

Figliolini

Tapparo

et al. 2020

Sci Rep

View full text Add to dashboard Cite

Serum-derived extracellular vesicles (sEV) from healthy donors display in-vivo pro-angiogenic properties. To identify patients that may benefit from autologous sEV administration for pro-angiogenic purposes, sEV angiogenic capability has been evaluated in type 2 diabetic (T2DM) subjects (D), in obese individuals with (OD) and without (O) T2DM, and in subjects with ischemic disease (IC) (9 patients/ group). sEV display different angiogenic properties in such cluster of individuals. miRNomic profile and tGfβ content in sEV were evaluated. We found that miR-130a and TGFβ content correlates with sEV in-vitro and in-vivo angiogenic properties, particularly in T2DM patients. Ingenuity Pathway Analysis (IPA) identified a number of genes as among the most significant miR-130a interactors. Gain-of-function experiments recognized homeoboxA5 (HOXA5) as a miR-130a specific target. Finally, ROC curve analyses revealed that sEV ineffectiveness could be predicted (Likelihood Ratio+ (LH+) = 3.3 IC 95% from 2.6 to 3.9) by comparing miR-130a and TGFβ content 'in Series'. We demonstrate that sEV from high cardiovascular risk patients have different angiogenic properties and that miR-130a and TGFβ sEV content predicts 'true ineffective sEVs'. These results provide the rationale for the use of these assays to identify patients that may benefit from autologous sEV administration to boost the angiogenetic process. Cardiovascular complications are relevant causes of morbidity and mortality in patients with diabetes and obesity 1. Recent evidence suggests that extracellular vesicles (EVs) may act as mediators of many pathophysiological processes 2-4. EVs are small vesicles that are released from different cell types under normal and pathological conditions 5,6. Increased levels of circulating EVs have been associated with vascular impairment and hypercoagulability, particularly in patients with diabetes and acute coronary syndrome, suggesting that they play a role in driving cardiovascular diseases 7,8. Moreover, increased levels of circulating EVs, mainly from platelets and endothelial cells, has been proposed as a hallmark of cell dysfunction 9. It has been extensively reported that EVs act as biological active vectors, and participate in the exchange of information between circulating and resident cells, including endothelial cells 2,10. It has also been proposed that platelet-derived EVs play a role in the pathogenesis of atherosclerosis 11. EVs act as biological intermediaries, and mainly do so by delivering proteins, active lipids and extracellular RNAs 12. However, the most frequently studied EV-mediated biological processes rely on microRNA (miRNA) transfer. miRNAs are a class of small noncoding RNAs post-transcriptionally regulating gene expression 13. miR-NAs are present in serum/plasma and it has been proposed that their distinctive expression patterns serve as disease fingerprints in many clinical settings 14. Moreover, it has been shown that activated platelets can transfer

show abstract

Section: Discussionmentioning

confidence: 99%

“…There is a growing body of evidence to suggest that EVs can act as potential therapeutic, diagnostic and prognostic tools 19,20 . We have previously developed an in-vitro test of potency to predict healthy subject-derived serum-EV (sEV) pro-angiogenic properties 21 .…”

mentioning

confidence: 99%

miR-130a and Tgfβ Content in Extracellular Vesicles Derived from the Serum of Subjects at High Cardiovascular Risk Predicts their In-Vivo Angiogenic Potential

Cavallari

Figliolini

Tapparo

et al. 2020

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Serum‐free conditioned medium was collected after treatment of ECs. Exosomes were also isolated with the ExoQuick Plasma prep and the Exosomes Precipitation Kit according to the manufacturer's instructions (System Biosciences) …”

Section: Methodsmentioning

confidence: 99%

Exosome derived from CD137‐modified endothelial cells regulates the Th17 responses in atherosclerosis

Geng

Zang

et al. 2020

J Cellular Molecular Medi

View full text Add to dashboard Cite

| 4659 wileyonlinelibrary.com/journal/jcmm 1 | INTRODUC TI ON T helpers 17 (Th17) cells have been identified as a new subset of lymphocytes which are shown to promote atherosclerosis (AS), and their associated cytokines in the pathogenesis of AS appear to be contradictory at first glance. 1-3 Recently, growing attention has been paid to the relative contribution of the local vs. peripheral inflammation to the procession of AS. Here, we focused on the communication between peripheral inflammation and vascular inflammation of Th17 cell differentiation during AS.Exosomes are a subset of extracellular vesicles (EVs) released by almost all types of cells, and they play a significant role in cellular proliferation, apoptosis, stress response and differentiation in the initial stage and development of AS. 4,5 In the present study, we investigated exosome-mediated cell-to-cell communication, which induced Th17 cell differentiation and promoted progression of the atherosclerotic plaque. AbstractThe role of exosomes derived from endothelial cells (ECs) in the progression of atherosclerosis (AS) and inflammation remains largely unexplored. We aimed to investigate whether exosome derived from CD137-modified ECs (CD137-Exo) played a major role in AS and to elucidate the potential mechanism underlying the inflammatory effect. Exosomes derived from mouse brain microvascular ECs treated with agonist anti-CD137 antibody were used to explore the effect of CD137 signalling in AS and inflammation in vitro and vivo. CD137-Exo efficiently induced the progression of AS in ApoE −/− mice. CD137-Exo increased the proportion of Th17 cells both in vitro and vivo. The IL-6 contained in CD137-Exo which is regulated by Akt and NF-КB pathway was verified to activate Th17 cell differentiation. IL-17 increased apoptosis, inhibited cell viability and improved lactate dehydrogenase (LDH) release in ECs subjected to inflammation induced by lipopolysaccharide (LPS). The expression of soluble intercellular adhesion molecule1 (sICAM-1), monocyte chemoattractant protein-1 (MCP-1) and E-selectin in the supernatants of ECs after IL-17 treatment was dramatically increased. CD137-Exo promoted the progression of AS and Th17 cell differentiation via NF-КB pathway mediated IL-6 expression. This finding provided a potential method to prevent local and peripheral inflammation in AS. K E Y W O R D S atherosclerosis, endothelial cells; Th17 cells, exosomes

show abstract

“…Additionally, it has been found that exercise can induce cardiomyocytes to release EVs/EXs, which exert a cardioprotective function in MI. A recent study showed that the serum level of EVs was increased by about 1.85-fold in mice after 3 weeks of swimming (Bei et al, 2017). Furthermore, intramyocardial injection of EVs induced by exercise exerted additional anti-apoptotic effects on H 2 O 2 -treated H9C2 cardiomyocytes compared to exercise alone.…”

Section: Novel Secretory Mechanisms Of Exercise-induced Cardioprotectmentioning

confidence: 98%

“…Intriguingly, circulatory EVs/EXs content varies in an intensity-dependent manner in response to exercise training (Bei et al, 2017). The heart is the main endocrine organ affected during exercise, and some cardiac-derived protective factors can be induced by exercise and carried by EVs/EXs to ameliorate the pathological processes of MI (Ogawa and de Bold, 2014;Sanchis-Gomar et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Novel Mechanisms of Exercise-Induced Cardioprotective Factors in Myocardial Infarction

2020

View full text Add to dashboard Cite

Exercise training has been reported to ameliorate heart dysfunction in both humans and animals after myocardial infarction (MI). Exercise-induced cardioprotective factors have been implicated in mediating cardiac repair under pathological conditions. These protective factors secreted by or enriched in the heart could exert cardioprotective functions in an autocrine or paracrine manner. Extracellular vesicles, especially exosomes, contain key molecules and play an essential role in cell-to-cell communication via delivery of various factors, which may be a novel target to study the mechanism of exercise-induced benefits, besides traditional signaling pathways. This review is designed to demonstrate the function and underlying protective mechanism of exercise-induced cardioprotective factors in MI, with an aim to offer more potential therapeutic targets for MI.

show abstract

Exercise-induced circulating extracellular vesicles protect against cardiac ischemia–reperfusion injury

Cited by 149 publications

References 50 publications

miR-130a and Tgfβ Content in Extracellular Vesicles Derived from the Serum of Subjects at High Cardiovascular Risk Predicts their In-Vivo Angiogenic Potential

miR-130a and Tgfβ Content in Extracellular Vesicles Derived from the Serum of Subjects at High Cardiovascular Risk Predicts their In-Vivo Angiogenic Potential

Exosome derived from CD137‐modified endothelial cells regulates the Th17 responses in atherosclerosis

Novel Mechanisms of Exercise-Induced Cardioprotective Factors in Myocardial Infarction

Contact Info

Product

Resources

About