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Altered cargo proteins of human plasma endothelial cell-derived exosomes in atherosclerotic cerebrovascular disease.

ABSTRACT: Plasma endothelial cell-derived exosomes (EDEs) and platelet-derived exosomes (PDEs) were precipitated and enriched separately by immunospecific absorption procedures for analyses of cargo proteins relevant to atherosclerosis. EDEs had usual exosome size and marker protein content, and significantly higher levels than PDEs of the endothelial proteins vascular cell adhesion molecule-1 (VCAM-1) and endothelial nitric oxide synthase, whereas PDEs had significantly higher levels of platelet glycoprotein VI. EDE levels of VCAM-1, von Willebrand factor, platelet-derived growth factor (PDGF)-BB, angiopoietin-1, and lysyl oxidase-2 and the cerebrovascular-selective proteins glucose transporter 1, permeability-glycoprotein, and large neutral amino acid transporter 1 were significantly higher for 18 patients with cerebrovascular disease (CeVD) than for 18 age- and gender-matched control subjects. PDE levels of PDGF-AA, platelet glycoprotein VI, integrin-linked kinase-1, high mobility group box-1 protein, chemokine CXCL4, and thrombospondin-1 were significantly higher in patients with CeVD than in control subjects, but differences were less with greater overlaps than for EDE proteins. EDE levels of Yes-associated protein (YAP) were higher and of P(S127)-YAP lower in patients with CeVD than in control subjects, consistent with heightened activity of this mechanical force-sensitive system in atherosclerosis. Elevated EDE and PDE levels of atherosclerosis-promoting proteins in CeVD justify clinical studies of their potential value as biomarkers.-Goetzl, E. J., Schwartz, J. B., Mustapic, M., Lobach, I. V., Daneman, R., Abner, E. L., Jicha, G. A. Altered cargo proteins of human plasma endothelial cell-derived exosomes in atherosclerotic cerebrovascular disease.

SUBMITTER: Goetzl EJ

PROVIDER: S-EPMC5503715 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Altered cargo proteins of human plasma endothelial cell-derived exosomes in atherosclerotic cerebrovascular disease.

Goetzl Edward J EJ Schwartz Janice B JB Mustapic Maja M Lobach Iryna V IV Daneman Richard R Abner Erin L EL Jicha Gregory A GA

FASEB journal : official publication of the Federation of American Societies for Experimental Biology 20170505 8

Plasma endothelial cell-derived exosomes (EDEs) and platelet-derived exosomes (PDEs) were precipitated and enriched separately by immunospecific absorption procedures for analyses of cargo proteins relevant to atherosclerosis. EDEs had usual exosome size and marker protein content, and significantly higher levels than PDEs of the endothelial proteins vascular cell adhesion molecule-1 (VCAM-1) and endothelial nitric oxide synthase, whereas PDEs had significantly higher levels of platelet glycopro ...[more]

PMID: 28476896

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Project description:Primary Sjögren's syndrome (pSS) is an autoimmune disease represented by exocrine gland epithelial cell lesions. However, the mechanism underlying these lesions remains unclear. This study analyzed the plasma exosomes of pSS patients using proteomics and revealed the presence of 24 differentially expressed proteins (DEPs) involved in the primary biological processes and signaling pathways related to ferroptosis. The DEPs enriched in the ferroptosis-related items were represented by downregulated ceruloplasmin (CP) and transferrin (TF). CC analysis of GO enrichment showed that CP and TF were localized at the apical plasma membrane, which is currently found only in epithelial cells. PPI analysis indicated that these exosomal DEPs formed a clustering network containing CP and TF. Among them, C5, C9, Haptoglobin (HP), and SERPING1 interacted directly with CP and TF. Notably, the expression of these proteins significantly decreased in both the pSS and secondary Sjögren's syndrome (sSS) plasma exosomes but not in non-autoimmune sicca syndrome (nSS). In addition, their expression levels were significantly different in the exosomes and plasma. More importantly, the plasma and salivary exosomes of pSS patients contain higher levels of exocrine gland epithelial autoantigens SSA and SSB than those of healthy controls, and epithelial cells with positive labial glands biopsy (LGB) were more susceptible to ferroptosis than those with negative LGB. The results indicated that ferroptosis may be closely related to SS epithelial cell lesions. KEY MESSAGES: • pSS plasma exosomes contain epithelial cell-derived proteins involved in ferroptosis. • Complement C5 and C9 may be new molecules involved in ferroptosis and play a crucial role in pSS epithelial cell pathology. • The serum exosomes from pSS patients, not nSS patients, contain ferroptosis-related proteins. • The changes in the ferroptosis-related protein content in the exosomes can better reflect the state of the epithelial cell lesions than those in the plasma.

Dataset Information

Altered cargo proteins of human plasma endothelial cell-derived exosomes in atherosclerotic cerebrovascular disease.

Publications

Altered cargo proteins of human plasma endothelial cell-derived exosomes in atherosclerotic cerebrovascular disease.

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