Significance of Extracellular Vesicles: Pathobiological Roles in Disease

Yamamoto, Seiji; Azuma, Erika; Matsushima, Masashi; Hamashima, Takeru; Ikoma, Yoko; Sasahara, Masakiyo

doi:10.1247/csf.16014

Cited by 45 publications

(44 citation statements)

References 64 publications

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“…Whether EVs can accelerate disease progression or induce vascular protection is still a matter of debate. Numerous evidence has shown that EVs can play a major role in inflammation, thrombosis and coagulation‐all of which are conditions that are involved in atherogenesis . However, recent data challenged the presumed deleterious role of EVs and suggested that EVs promote cell survival, exert anti‐inflammatory effects, counteract coagulation processes or induce endothelial regeneration .…”

Section: Introductionmentioning

confidence: 99%

“…Numerous evidence has shown that EVs can play a major role in inflammation, thrombosis and coagulation-all of which are conditions that are involved in atherogenesis. [13][14][15][16] However, recent data challenged the presumed deleterious role of EVs and suggested that EVs promote cell survival, exert anti-inflammatory effects, counteract coagulation processes or induce endothelial regeneration. 17,18 Taken together, the role of EVs in the maintenance of vascular homeostasis is more complex than initially considered.…”

Section: Introductionmentioning

confidence: 99%

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Endothelial extracellular vesicles modulate the macrophage phenotype: Potential implications in atherosclerosis

Xiao

et al. 2018

Scand J Immunol

100

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Endothelial cells (ECs) and macrophages engage in tight and specific interactions that play critical roles in cardiovascular homeostasis and the pathogenesis of atherosclerosis. Extracellular vesicles (EVs) are circular membrane fragments released from the endosomal compartment as exosomes or shed from the surfaces of the membranes of most cell types. Increasing evidence indicates that EVs play a pivotal role in cell-to-cell communication. However, the contribution of EVs, as determine by oxidized low-density lipoprotein (ox-LDL)-exposed and/or Kruppel-like factor 2 (KLF2)-transduced ECs in the interaction between vascular ECs and monocytes/macrophages, which is a key event in atherosclerotic plaque development, has remained elusive. This study demonstrates the characteristic impact of EVs from ox-LDL-treated and/or KLF2-transduced ECs on the monocyte/macrophage phenotype in vitro and in vivo.Q-PCR showed that both the atherosclerosis inducer ox-LDL and atheroprotective factor KLF2 regulated inflammation-associated microRNA-155 (miR-155) expression in human umbilical vein endothelial cells (HUVECs). Moreover, coculture, immunofluorescence and flow cytometry revealed that miR-155 was enriched in ox-LDL-induced ECs-EVs and subsequently transferred to human monocytic THP1 cells, in which these vesicles enhance monocyte activation by shifting the monocytes/macrophages balance from anti-inflammatory M2 macrophages towards proinflammatory M1 macrophages; EVs from KLF2-expressing ECs suppressed monocyte activation by enhancing immunomodulatory responses and diminishing proinflammatory responses, which indicate the potent anti-inflammatory activities of these cells. Furthermore, oil red staining showed that atherosclerotic lesions were reduced in mice that received EVs from KLF2-transduced ECs with decreased proinflammatory M1 macrophages and increased anti-inflammatory M2 macrophages, and this effect is at least partly due to the decreased expression of inflammation-associated miR-155, confirming our in vitro findings. In summary, this study provides novel insights into the pathophysiological effects of altered EV secretion and/or microRNA content and their influence on modulating monocyte activation depending on the environment surrounding EVs-releasing ECs.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Endothelial extracellular vesicles modulate the macrophage phenotype: Potential implications in atherosclerosis

Xiao

et al. 2018

Scand J Immunol

100

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“…; Cocucci & Meldolesi, ; Shintaku & Maeno, ; Yamamoto et al. ). Molecular mechanisms involved in the release of these vesicles as well as conditions influencing the occurrence of blebbing (Tokuda et al.…”

Section: Discussionmentioning

confidence: 99%

Regulation of apical blebbing in the porcine epididymis

Hughes

Berger

2017

Journal of Anatomy

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Apical blebbing, a non-classical secretion mechanism, occurs in the mature porcine epididymis as part of its normal function. Proteins secreted by this mechanism contribute to the modification of the sperm plasma membrane during epididymal transit and are thought to contribute to acquisition of fertilizing ability. However, little is known about the regulation of this secretion mechanism in an in vivo model. Previous work demonstrated apical blebbing in the epididymis developed pubertally, suggesting androgens, sperm or other luminal factors regulated this process. Hence, the objective was to evaluate the hypothesized regulation of apical blebbing in the epididymis of pubertal boars by androgens and luminal factors. Androgen receptor blockade (flutamide) and surgical interventions (efferent duct ligation, orchidectomy or transection of the caput epididymis) were used to alter signaling, and the subsequent effects on apical blebbing were evaluated histologically. Apical blebbing was not altered by androgen receptor blockade with flutamide, but was significantly reduced 24 h after efferent duct ligation and after orchidectomy, treatments that eliminated luminal flow from the testis (P < 0.05). Like efferent duct ligation, epididymal transection altered luminal flow without removing the androgen source and significantly reduced the appearance of apical blebbing (P < 0.05). In conclusion, apical blebbing in the porcine epididymis appears to be regulated by luminal factors.

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“…Internucleosomal fragmentation of chromatin is performed by speciic apoptotic nucleases during early phase of the process [45]. Nuclear antigens, including nucleosomes, moved then to litle bulbs of cell membrane, so-called apoptotic bodies [46]. Interestingly, in some virus infections, endogenous nucleoproteins are bundled together with virions and, thereby, can be jointly presented in apoptotic bodies [47].…”

Section: Normal Generation and Clearance Of Extracellular Dnamentioning

confidence: 99%

Elimination of Nucleoproteins in Systemic Lupus Erythematosus and Antinuclear Autoantibodies Production

Trofimenko¹

2017

Lupus

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The distinctive feature of systemic lupus erythematosus (SLE) is an immune reaction directed to diverse spectrum of autoantigens, which tends to change along with the disease spreading. The most common targets of the autoantibodies are protein and nucleoprotein components of cell nuclei: dsDNA, histones, nucleosomes, Sm antigen, and Ro and La antigens. Considering that the exact causes of this tolerance loss are unknown, a certain number of hypotheses are now discussed. One of the most promising is "waste disposal" concept, which makes a link between broken elimination of cellular debris, mononuclear phagocyte system dysfunction, and initiation of autoimmunity by the antigen presenting cells in SLE. This chapter concerns the ways nuclear antigens release from cells, necrosis, and apoptosis, as well as the key molecular mechanisms of transport and elimination of these antigens, its disturbances in SLE, and connection with innate immunity by mononuclear cells. Special atention is paid to nucleosomes and DNA degradation process, its principal factors (DNase I, C1q, SAP), blood DNA transportation by immune complexes, and immune stimulating action of DNA in SLE. Current pros and cons for the waste disposal concept and existing research trends in this ield are discussed.

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Significance of Extracellular Vesicles: Pathobiological Roles in Disease

Cited by 45 publications

References 64 publications

Endothelial extracellular vesicles modulate the macrophage phenotype: Potential implications in atherosclerosis

Endothelial extracellular vesicles modulate the macrophage phenotype: Potential implications in atherosclerosis

Regulation of apical blebbing in the porcine epididymis

Elimination of Nucleoproteins in Systemic Lupus Erythematosus and Antinuclear Autoantibodies Production

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