Extracellular vesicle secretion is tissue-dependent ex vivo and skeletal muscle myofiber extracellular vesicles reach the circulation in vivo

Estrada, Andrea; Valenti, Zackary J.; Hehn, Gabriella; Amorese, Adam J.; Williams, Nicholas S.G.; Balestrieri, Nicholas P.; Deighan, Clayton; Allen, Christopher P.; Spangenburg, Espen E.; Kruh-Garcia, Nicole A.; Lark, Daniel S.

doi:10.1152/ajpcell.00580.2020

Cited by 51 publications

(69 citation statements)

References 39 publications

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“…Acute resistance exercise can alter circulating miRNA (increase in miR‐149; decrease in miR‐146a) at 3 days, but not at 0 h, 1 h or 1 day postexercise (Sawada et al., 2013). It appears that increases in circulating small EVs, hence miRNA, in response to exercise are not derived from skeletal muscle (Estrada et al., 2022). Increases in skeletal muscle mass with obesity are important to maintain mobility; however, uncontrolled hypertrophy could result in inadequate vascularization and substrate delivery.…”

Section: Discussionmentioning

confidence: 99%

Effects of obesity and acute resistance exercise on skeletal muscle angiogenic communication pathways

Garner

Weiss

Nie

et al. 2022

Experimental Physiology

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Obesity (OB) impairs cell-to-cell communication signalling. Small extracellular vesicles (EVs), which include exosomes, are released by skeletal muscle and participate in cellto-cell communication, including the regulation of angiogenesis. Resistance exercise (REx) increases muscle fibre size and capillarization. Although obesity increases muscle fibre size, there is an inadequate increase in capillarization such that capillary density is reduced. It was hypothesized that REx-induced angiogenic signalling and EV biogenesis would be lower with obesity. Sedentary lean (LN) and OB subjects (n = 8 per group) performed three sets of single-leg knee-extension REx at 80% of maximum. Muscle biopsies were obtained at rest, 15 min and 3 h postexercise and analysed for angiogenic and EV biogenesis mRNA and protein. In OB subjects, muscle fibre size was ∼20% greater and capillary density with type II fibres ∼25% lower compared with LN subjects (P < 0.001). In response to REx, the increase in VEGF mRNA (pro-angiogenic) was similar (3-fold) between groups, while thrombospondin-1 (TSP-1) mRNA (anti-angiogenic) increased ∼2.5-fold in OB subjects only (P = 0.010). miR-130a (pro-angiogenic) was ∼1.4-fold (P = 0.011) and miR-503 (anti-angiogenic) ∼1.8-fold (P = 0.017) greater in OB compared with LN subjects at all time points. In both groups, acute REx decreased the EV surface protein Alix by ∼50%, consistent with the release of exosomes (P = 0.016). Acute REx appears to induce the release of skeletal muscle small EVs independent of body mass. However, with obesity there is predominantly impaired angiogenic signalling, consistent with inadequate angiogenesis in response to basal muscle hypertrophy.

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Section: Discussionmentioning

confidence: 99%

Effects of obesity and acute resistance exercise on skeletal muscle angiogenic communication pathways

Garner

Weiss

Nie

et al. 2022

Experimental Physiology

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“…We know that EV levels can be impacted by sex [ 290 ], age [ 291 ], pregnancy [ 292 ], a high-fat meal [ 293 ], and exercise intensity [ 294 , 295 , 296 ]. Indeed, skeletal muscle myofibers are a major source of EVs, more than white adipose tissue, that can reach the circulation in vivo [ 297 ]. Large clinical trials to fully demonstrate EV potential are an indispensable pre-requisite before entering the clinical arena.…”

Section: Extracellular Vesicles As Diagnostic and Prognostic Biomarkersmentioning

confidence: 99%

Extracellular Vesicles as Drivers of Immunoinflammation in Atherothrombosis

Suades

Greco

Padró

et al. 2022

Cells

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Atherosclerotic cardiovascular disease is the leading cause of morbidity and mortality all over the world. Extracellular vesicles (EVs), small lipid-bilayer membrane vesicles released by most cellular types, exert pivotal and multifaceted roles in physiology and disease. Emerging evidence emphasizes the importance of EVs in intercellular communication processes with key effects on cell survival, endothelial homeostasis, inflammation, neoangiogenesis, and thrombosis. This review focuses on EVs as effective signaling molecules able to both derail vascular homeostasis and induce vascular dysfunction, inflammation, plaque progression, and thrombus formation as well as drive anti-inflammation, vascular repair, and atheroprotection. We provide a comprehensive and updated summary of the role of EVs in the development or regression of atherosclerotic lesions, highlighting the link between thrombosis and inflammation. Importantly, we also critically describe their potential clinical use as disease biomarkers or therapeutic agents in atherothrombosis.

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“…Recent evidence indicates that EVs exert endocrine effects in addition to their potent paracrine effects (Rome et al., 2019). However, the extent of these endocrine effects is likely to be limited, because only 5% of circulating EVs are of myogenic origin despite the robust ability of skeletal muscle to secrete EVs, (Estrada et al., 2021). After intraperitoneal injection in mice, skeletal muscle‐derived EVs can be found within cells of at least eight different organs in addition to skeletal muscle, including brain, liver, heart, lungs, gastrointestinal tract, spleen, kidney and pancreas (Jalabert et al., 2016).…”

Section: Discussionmentioning

confidence: 99%

“…However, the extent of these endocrine effects is likely to be limited, because only 5% of circulating EVs are of myogenic origin despite the robust ability of skeletal muscle to secrete EVs, (Estrada et al, 2021).…”

Section: Exercise Training Alters Ev Mirnas Targeting Inflammationmentioning

confidence: 99%

Obesity and exercise training alter inflammatory pathway skeletal muscle small extracellular vesicle microRNAs

Sullivan

Nie

Evans

et al. 2022

Experimental Physiology

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New Findings What is the central question of this study?Is 1 week of exercise training sufficient to reduce local and systemic inflammation?Do obesity and short‐term concurrent aerobic and resistance exercise training alter skeletal muscle extracellular vesicle (EV) contents? What is the main finding and its importance?Obesity alters skeletal muscle small EV microRNAs targeting inflammatory and growth pathways. Exercise training alters skeletal muscle small EV microRNAs targeting inflammatory pathways, indicative of reduced inflammation. Our findings provide support for the hypotheses that EVs play a vital role in intercellular communication during health and disease and that EVs mediate many of the beneficial effects of exercise. Abstract Obesity is associated with chronic inflammation characterized by increased levels of inflammatory cytokines, whereas exercise training reduces inflammation. Small extracellular vesicles (EVs; 30–150 nm) participate in cell‐to‐cell communication in part through microRNA (miRNA) post‐transcriptional regulation of mRNA. We examined whether obesity and concurrent aerobic and resistance exercise training alter skeletal muscle EV miRNA content and inflammatory signalling. Vastus lateralis biopsies were obtained from sedentary individuals with (OB) and without obesity (LN). Before and after 7 days of concurrent aerobic and resistance training, muscle‐derived small EV miRNAs and whole‐muscle mRNAs were measured. Pathway analysis revealed that obesity alters small EV miRNAs that target inflammatory (SERPINF1, death receptor and Gαi) and growth pathways (Wnt/β‐catenin, PTEN, PI3K/AKT and IGF‐1). In addition, exercise training alters small EV miRNAs in an anti‐inflammatory manner, targeting the IL‐10, IL‐8, Toll‐like receptor and nuclear factor‐κB signalling pathways. In whole muscle, IL‐8 mRNA was reduced by 50% and Jun mRNA by 25% after exercise training, consistent with the anti‐inflammatory effects of exercise on skeletal muscle. Obesity and 7 days of concurrent exercise training differentially alter skeletal muscle‐derived small EV miRNA contents targeting inflammatory and anabolic pathways.

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Extracellular vesicle secretion is tissue-dependent ex vivo and skeletal muscle myofiber extracellular vesicles reach the circulation in vivo

Cited by 51 publications

References 39 publications

Effects of obesity and acute resistance exercise on skeletal muscle angiogenic communication pathways

Effects of obesity and acute resistance exercise on skeletal muscle angiogenic communication pathways

Extracellular Vesicles as Drivers of Immunoinflammation in Atherothrombosis

Obesity and exercise training alter inflammatory pathway skeletal muscle small extracellular vesicle microRNAs

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