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

Edward J. Goetzl; J. B. Schwartz; Maja Mustapic; Iryna V. Lobach; Richard Daneman; Erin L. Abner; Gregory A. Jicha

doi:10.1096/fj.201700149

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

Edward J. Goetzl, J. B. Schwartz, Maja Mustapic, Iryna V. Lobach, Richard Daneman, Erin L. Abner, Gregory A. Jicha

Research output: Contribution to journal › Article › peer-review

60 Scopus citations

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. FASEB J. 31, 3689–3694 (2017). www.fasebj.org

Original language	English
Pages (from-to)	3689-3694
Number of pages	6
Journal	FASEB Journal
Volume	31
Issue number	8
DOIs	https://doi.org/10.1096/fj.201700149
State	Published - Aug 2017

Bibliographical note

Funding Information:
This work was supported by a grant from the Biomarkers Across Neurodegenerative Diseases 2 (BAND2) Program of the Michael J. Fox Foundation for Parkinson’s Research, Alzheimer’s Association, Alzheimer’s Research UK and the Weston Brain Institute (to E.J.G.), and by Grant R01 NR014189 from the U.S. National Institutes of Health (NIH) National Institute for Nursing Research (to G.A.J.). M.M. was supported by the Intramural Research Program of the NIH National Institute on Aging. The authors thank Judith H. Goetzl (Jewish Home of San Francisco) for expert preparation of the illustrations. E.J.G. has filed an application with the U.S. Patent Office for the platform and methodologies described in this report. All remaining authors declare no conflicts of interest

Publisher Copyright:
© FASEB

Keywords

Angiogenesis
Blood biomarkers
Cellular adhesion
Platelets
Stroke

ASJC Scopus subject areas

Biotechnology
Biochemistry
Molecular Biology
Genetics

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1096/fj.201700149

Cite this

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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. FASEB J. 31, 3689–3694 (2017). www.fasebj.org",

keywords = "Angiogenesis, Blood biomarkers, Cellular adhesion, Platelets, Stroke",

author = "Goetzl, {Edward J.} and Schwartz, {J. B.} and Maja Mustapic and Lobach, {Iryna V.} and Richard Daneman and Abner, {Erin L.} and Jicha, {Gregory A.}",

note = "Funding Information: This work was supported by a grant from the Biomarkers Across Neurodegenerative Diseases 2 (BAND2) Program of the Michael J. Fox Foundation for Parkinson{\textquoteright}s Research, Alzheimer{\textquoteright}s Association, Alzheimer{\textquoteright}s Research UK and the Weston Brain Institute (to E.J.G.), and by Grant R01 NR014189 from the U.S. National Institutes of Health (NIH) National Institute for Nursing Research (to G.A.J.). M.M. was supported by the Intramural Research Program of the NIH National Institute on Aging. The authors thank Judith H. Goetzl (Jewish Home of San Francisco) for expert preparation of the illustrations. E.J.G. has filed an application with the U.S. Patent Office for the platform and methodologies described in this report. All remaining authors declare no conflicts of interest Publisher Copyright: {\textcopyright} FASEB",

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language = "English",

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AU - Daneman, Richard

AU - Abner, Erin L.

AU - Jicha, Gregory A.

N1 - Funding Information: This work was supported by a grant from the Biomarkers Across Neurodegenerative Diseases 2 (BAND2) Program of the Michael J. Fox Foundation for Parkinson’s Research, Alzheimer’s Association, Alzheimer’s Research UK and the Weston Brain Institute (to E.J.G.), and by Grant R01 NR014189 from the U.S. National Institutes of Health (NIH) National Institute for Nursing Research (to G.A.J.). M.M. was supported by the Intramural Research Program of the NIH National Institute on Aging. The authors thank Judith H. Goetzl (Jewish Home of San Francisco) for expert preparation of the illustrations. E.J.G. has filed an application with the U.S. Patent Office for the platform and methodologies described in this report. All remaining authors declare no conflicts of interest Publisher Copyright: © FASEB

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N2 - 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. FASEB J. 31, 3689–3694 (2017). www.fasebj.org

AB - 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. FASEB J. 31, 3689–3694 (2017). www.fasebj.org

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KW - Blood biomarkers

KW - Cellular adhesion

KW - Platelets

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

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