Internalization and induction of antioxidant messages by microvesicles contribute to the antiapoptotic effects on human endothelial cells

Soleti, Raffaella; Lauret, Emilie; Andriantsitohaina, Ramaroson; Martínez, María Carmen

doi:10.1016/j.freeradbiomed.2012.09.021

Cited by 46 publications

(42 citation statements)

References 30 publications

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“…Some detected no antioxidant proteins [47, 48] while others reported them to contain GPX, GST, PRDX1–3, and SOD2 [49]; GPX, PRDX5, TRX, and SOD2 [50]; GST, SOD2, and PRDX6 [51]; and GPX3, PRX1, PRX2, and PRX4 [52]. CAT and the three SOD isoforms have also been reported to be present and functional in HUVEC MVs [53]. SOD2, TRX, TRXR, and CAT have also been detected in the MVs of Cryptococcus neoformans , a unicellular eukaryote parasite [54].…”

Section: Discussionmentioning

confidence: 99%

“…The present results also show HUVEC-derived MVs to contain components of these antioxidant systems that might help endothelial cells in their regulation of blood plasma redox status. A functional role as protectors against oxidative stress was suggested by Soleti et al [53]. Later, experimental treatments were devised using EVs to reduce oxidative stress in the injured kidney [40, 41] and in experimental colitis [42].…”

Section: Discussionmentioning

confidence: 99%

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The Antioxidant Machinery of Young and Senescent Human Umbilical Vein Endothelial Cells and Their Microvesicles

Bodega

Alique

Bohórquez

et al. 2017

Oxidative Medicine and Cellular Longevity

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We examine the antioxidant role of young and senescent human umbilical vein endothelial cells (HUVECs) and their microvesicles (MVs). Proteomic and Western blot studies have shown young HUVECs to have a complete and well-developed antioxidant system. Their MVs also contain antioxidant molecules, though of a smaller and more specific range, specialized in the degradation of hydrogen peroxide and the superoxide anion via the thioredoxin-peroxiredoxin system. Senescence was shown to be associated with a large increase in the size of the antioxidant machinery in both HUVECs and their MVs. These responses might help HUVECs and their MVs deal with the more oxidising conditions found in older cells. Functional analysis confirmed the antioxidant machinery of the MVs to be active and to increase in size with senescence. No glutathione or nonpeptide antioxidant (ascorbic acid and vitamin E) activity was detected in the MVs. Endothelial cells and MVs seem to adapt to higher ROS concentrations in senescence by increasing their antioxidant machinery, although this is not enough to recover completely from the senescence-induced ROS increase. Moreover, MVs could be involved in the regulation of the blood plasma redox status by functioning as ROS scavengers.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The Antioxidant Machinery of Young and Senescent Human Umbilical Vein Endothelial Cells and Their Microvesicles

Bodega

Alique

Bohórquez

et al. 2017

Oxidative Medicine and Cellular Longevity

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show abstract

“…In order to co-culture HBVSMC with EMV, the latter were labeled with PKH26 (Sigma Aldrich, St Louis, MO) according to the manufacturer's protocol with some modifications (Soleti et al, 2012). Briefly, the concentration of EMV was quantified by NTA, and 2 × 10 7 /mL EMV were used for co-culture experiments.…”

Section: Methodsmentioning

confidence: 99%

Microvesicles Derived from Inflammation-Challenged Endothelial Cells Modulate Vascular Smooth Muscle Cell Functions

et al. 2017

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Purpose: Microvesicles (MV) can modulate the function of recipient cells by transferring their contents. Our previous study highlighted that MV released from tumor necrosis factor-α (TNF-α) plus serum deprivation (SD)-stimulated endothelial progenitor cells, induce detrimental effects on endothelial cells. In this study, we investigated the potential effects of endothelial MV (EMV) on proliferation, migration, and apoptosis of human brain vascular smooth cells (HBVSMC).Methods: EMV were prepared from human brain microvascular endothelial cells (HBMEC) cultured in a TNF-α plus SD medium. RNase-EMV were made by treating EMV with RNase A for RNA depletion. The proliferation, apoptosis and migration abilities of HBVSMC were determined after co-culture with EMV or RNase-EMV. The Mek1/2 inhibitor, PD0325901, was used for pathway analysis. Western blot was used for analyzing the proteins of Mek1/2, Erk1/2, phosphorylation Erk1/2, activated caspase-3 and Bcl-2. The level of miR-146a-5p was measured by qRT-PCR.Results: (1) EMV significantly promoted the proliferation and migration of HBVSMC. The effects were accompanied by an increase in Mek1/2 and p-Erk1/2, which could be abolished by PD0325901; (2) EMV decreased the apoptotic rate of HBVSMC by approximately 35%, which was accompanied by cleaved caspase-3 down-regulation and Bcl-2 up-regulation; (3) EMV increased miR-146a-5p level in HBVSMC by about 2-folds; (4) RNase-treated EMV were less effective than EMV on HBVSMC activities and miR-146a-5p expression.Conclusion: EMV generated under inflammation challenge can modulate HBVSMC function and fate via their carried RNA. This is associated with activation of theMek1/2/Erk1/2 pathway and caspase-3/Bcl-2 regulation, during which miR-146a-5p may play an important role. The data suggest that EMV derived from inflammation-challenged endothelial cells are detrimental to HBVSMC homeostatic functions, highlighting potential novel therapeutic targets for vascular diseases.

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“…Mechanistically, EVs Shh+ exert their vasculoprotective effects by promoting internalization and induction of antioxidant messages to the endothelial monolayer. Indeed, EVs Shh+ prevent apoptosis in endothelial cells induced by actinomycin D by transferring functional antioxidant enzymes [superoxide dismutase (SOD) isoforms and catalase] and by inducing cellular Mn-SOD protein expression (79). Anti-apoptotic effects have also been reported following Hh ligand treatment of endothelial cells, but rather relying on the inhibition of the pro-apoptotic effect of PTC, normally leading to caspase-3 cleavage (69).…”

Section: Evs Harboring Shh As Vascular and Cardio-protective Deliverymentioning

confidence: 99%

Extracellular Vesicles as Therapeutic Tools in Cardiovascular Diseases

2014

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Extracellular vesicles (EVs), including microvesicles (MVs) and exosomes, are small vesicles secreted from a wide variety of cells. Whereas MVs are particles released by the outward budding of the plasma membrane, exosomes are derived from endocytic compartments. Secretion of EVs can be enhanced by specific stimuli, and increased plasma circulating levels of EVs have been correlated with pathophysiological situations. MVs, already present in the blood of healthy individuals, are considerably elevated in several cardiovascular diseases associated with inflammation, suggesting that they can mediate deleterious effects such as endothelial dysfunction or thrombosis. Nonetheless, very recent studies also demonstrate that MVs may act as biological information vectors transferring proteins or genetic material to maintain cell homeostasis, favor cell repair, or even promote angiogenesis. Additionally, exosomes have also been shown to have pro-angiogenic and cardio-protective properties. These beneficial effects, therefore, reveal the potential therapeutical use of EVs in the field of cardiovascular medicine and regenerative therapy. In this review, we will provide an update of cellular processes modulated by EVs of specific interest in the treatment of cardiovascular pathologies. A special focus will be made on the morphogen sonic hedgehog (Shh) associated with EVs (EVsShh+), which have been shown to mediate many pro-angiogenic effects. In addition to offer a potential source of cardiovascular markers, therapeutical potential of EVs reveal exciting opportunities to deliver specific agents by non-immunogenic means to cardiovascular system.

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Internalization and induction of antioxidant messages by microvesicles contribute to the antiapoptotic effects on human endothelial cells

Cited by 46 publications

References 30 publications

The Antioxidant Machinery of Young and Senescent Human Umbilical Vein Endothelial Cells and Their Microvesicles

The Antioxidant Machinery of Young and Senescent Human Umbilical Vein Endothelial Cells and Their Microvesicles

Microvesicles Derived from Inflammation-Challenged Endothelial Cells Modulate Vascular Smooth Muscle Cell Functions

Extracellular Vesicles as Therapeutic Tools in Cardiovascular Diseases

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