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      Emerging role of exosome-mediated intercellular communication in vascular remodeling

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          Abstract

          Vascular remodeling refers to the alternations of function and structure in vasculature. A complex autocrine/paracrine set of cellular interaction is involved in vascular remodeling. Exosome, a newly identified natural nanocarrier and intercellular messenger, plays a pivotal role in regulating cell-to-cell communication. Exosome emerges as an important mediator in the process of vascular remodeling, showing the most prognostic and therapeutic potent in vascular diseases. Benefiting from exosomal trafficking, the vasculature can not only maintain its function and structure in physiological condition, but also adapt itself in pathological status. In this review, we will represent the roles of exosomes in angiogenesis, endothelial function and cardiac regeneration. In addition, greatly depending on the pathophysiological status of donor cells and peripheral micro-circumstance, the exosomal content could alter, which makes exosomes exhibit pleiotropic effects in vascular diseases. Hence, the diverse effects of exosomes in vascular diseases including atherosclerosis, neointima formation and vascular repair, primary hypertension, pulmonary artery hypertension, and aortic aneurysm will be discussed. Finally, the translational appliances targeting exosomes will be concluded by providing updated applications of engineered exosomes in clinic.

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          Most cited references62

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          A phase I study of dexosome immunotherapy in patients with advanced non-small cell lung cancer

          Background There is a continued need to develop more effective cancer immunotherapy strategies. Exosomes, cell-derived lipid vesicles that express high levels of a narrow spectrum of cell proteins represent a novel platform for delivering high levels of antigen in conjunction with costimulatory molecules. We performed this study to test the safety, feasibility and efficacy of autologous dendritic cell (DC)-derived exosomes (DEX) loaded with the MAGE tumor antigens in patients with non-small cell lung cancer (NSCLC). Methods This Phase I study enrolled HLA A2+ patients with pre-treated Stage IIIb (N = 4) and IV (N = 9) NSCLC with tumor expression of MAGE-A3 or A4. Patients underwent leukapheresis to generate DC from which DEX were produced and loaded with MAGE-A3, -A4, -A10, and MAGE-3DPO4 peptides. Patients received 4 doses of DEX at weekly intervals. Results Thirteen patients were enrolled and 9 completed therapy. Three formulations of DEX were evaluated; all were well tolerated with only grade 1–2 adverse events related to the use of DEX (injection site reactions (N = 8), flu like illness (N = 1), and peripheral arm pain (N = 1)). The time from the first dose of DEX until disease progression was 30 to 429+ days. Three patients had disease progression before the first DEX dose. Survival of patients after the first DEX dose was 52–665+ days. DTH reactivity against MAGE peptides was detected in 3/9 patients. Immune responses were detected in patients as follows: MAGE-specific T cell responses in 1/3, increased NK lytic activity in 2/4. Conclusion Production of the DEX vaccine was feasible and DEX therapy was well tolerated in patients with advanced NSCLC. Some patients experienced long term stability of disease and activation of immune effectors
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            Exosomes: a common pathway for a specialized function.

            Exosomes are membrane vesicles that are released by cells upon fusion of multivesicular bodies with the plasma membrane. Their molecular composition reflects their origin in endosomes as intraluminal vesicles. In addition to a common set of membrane and cytosolic molecules, exosomes harbor unique subsets of proteins linked to cell type-associated functions. Exosome secretion participates in the eradication of obsolete proteins but several findings, essentially in the immune system, indicate that exosomes constitute a potential mode of intercellular communication. Release of exosomes by tumor cells and their implication in the propagation of unconventional pathogens such as prions suggests their participation in pathological situations. These findings open up new therapeutic and diagnostic strategies.
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              Proteomic profiling of exosomes: current perspectives.

              Exosomes are 40-100 nm membrane vesicles of endocytic origin secreted by most cell types in vitro. Recent studies have shown that exosomes are also found in vivo in body fluids such as blood, urine, amniotic fluid, malignant ascites, bronchoalveolar lavage fluid, synovial fluid, and breast milk. While the biological function of exosomes is still unclear, they can mediate communication between cells, facilitating processes such as antigen presentation and in trans signaling to neighboring cells. Exosome-like vesicles identified in Drosophila (referred to as argosomes) may be potential vehicles for the spread of morphogens in epithelia. The advent of current MS-based proteomic technologies has contributed significantly to our understanding of the molecular composition of exosomes. In addition to a common set of membrane and cytosolic proteins, it is becoming increasingly apparent that exosomes harbor distinct subsets of proteins that may be linked to cell-type associated functions. The secretion of exosomes by tumor cells and their implication in the transport and propagation of infectious cargo such as prions and retroviruses such as HIV suggest their participation in pathological situations. Interestingly, the recent observation that exosomes contain both mRNA and microRNA, which can be transferred to another cell, and be functional in that new environment, is an exciting new development in the unraveling exosome saga. The present review aims to summarize the physical properties that define exosomes as specific cell-type secreted membrane vesicles.
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                Author and article information

                Journal
                Oncotarget
                Oncotarget
                Oncotarget
                ImpactJ
                Oncotarget
                Impact Journals LLC
                1949-2553
                11 April 2017
                28 January 2017
                : 8
                : 15
                : 25700-25712
                Affiliations
                1 Department of Cardiology, Cardiovascular Key Lab of Zhejiang Province, Second Affiliated Hospital, Zhejiang University College of Medicine, Hang Zhou, Zhejiang, P.R. China
                2 Cardiovascular Division, Kings College London BHF Center, London, United Kingdom
                Author notes
                Correspondence to: Meixiang Xiang, xiangmx@ 123456zju.edu.cn
                Article
                14878
                10.18632/oncotarget.14878
                5421963
                28147325
                c70f2a78-4662-4229-86db-12843182ad01
                Copyright: © 2017 Su et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC-BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 15 May 2016
                : 18 January 2017
                Categories
                Review

                Oncology & Radiotherapy
                exosome,vascular remodeling,endothelial function,atherosclerosis,vascular repair

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