Protein disulfide isomerase plasma levels in healthy humans reveal proteomic signatures involved in contrasting endothelial phenotypes
Redox-related plasma proteins are candidate reporters of protein signatures associated with endothelial structure/function. Thiol-proteins from protein disulfide isomerase (PDI) family are unexplored in this context. Here, we investigate the occurrence and physiological significance of a circulating...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2019-04-01
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| Series: | Redox Biology |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231719300217 |
| _version_ | 1818503064223481856 |
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| author | Percíllia Victória Santos de Oliveira Sheila Garcia-Rosa Ana Teresa Azevedo Sachetto Ana Iochabel Soares Moretti Victor Debbas Tiphany Coralie De Bessa Nathalia Tenguan Silva Alexandre da Costa Pereira Daniel Martins-de-Souza Marcelo Larami Santoro Francisco Rafael Martins Laurindo |
| author_facet | Percíllia Victória Santos de Oliveira Sheila Garcia-Rosa Ana Teresa Azevedo Sachetto Ana Iochabel Soares Moretti Victor Debbas Tiphany Coralie De Bessa Nathalia Tenguan Silva Alexandre da Costa Pereira Daniel Martins-de-Souza Marcelo Larami Santoro Francisco Rafael Martins Laurindo |
| author_sort | Percíllia Victória Santos de Oliveira |
| collection | DOAJ |
| description | Redox-related plasma proteins are candidate reporters of protein signatures associated with endothelial structure/function. Thiol-proteins from protein disulfide isomerase (PDI) family are unexplored in this context. Here, we investigate the occurrence and physiological significance of a circulating pool of PDI in healthy humans. We validated an assay for detecting PDI in plasma of healthy individuals. Our results indicate high inter-individual (median = 330 pg/mL) but low intra-individual variability over time and repeated measurements. Remarkably, plasma PDI levels could discriminate between distinct plasma proteome signatures, with PDI-rich (>median) plasma differentially expressing proteins related to cell differentiation, protein processing, housekeeping functions and others, while PDI-poor plasma differentially displayed proteins associated with coagulation, inflammatory responses and immunoactivation. Platelet function was similar among individuals with PDI-rich vs. PDI-poor plasma. Remarkably, such protein signatures closely correlated with endothelial function and phenotype, since cultured endothelial cells incubated with PDI-poor or PDI-rich plasma recapitulated gene expression and secretome patterns in line with their corresponding plasma signatures. Furthermore, such signatures translated into functional responses, with PDI-poor plasma promoting impairment of endothelial adhesion to fibronectin and a disturbed pattern of wound-associated migration and recovery area. Patients with cardiovascular events had lower PDI levels vs. healthy individuals. This is the first study describing PDI levels as reporters of specific plasma proteome signatures directly promoting contrasting endothelial phenotypes and functional responses. Keywords: Protein disulfide isomerase, Plasma proteome, Endothelial cells, Plasma protein signatures, Thiol proteins |
| first_indexed | 2024-12-10T21:18:50Z |
| format | Article |
| id | doaj.art-332b5527aa7043708192a2c0345653aa |
| institution | Directory Open Access Journal |
| issn | 2213-2317 |
| language | English |
| last_indexed | 2024-12-10T21:18:50Z |
| publishDate | 2019-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj.art-332b5527aa7043708192a2c0345653aa2022-12-22T01:33:10ZengElsevierRedox Biology2213-23172019-04-0122Protein disulfide isomerase plasma levels in healthy humans reveal proteomic signatures involved in contrasting endothelial phenotypesPercíllia Victória Santos de Oliveira0Sheila Garcia-Rosa1Ana Teresa Azevedo Sachetto2Ana Iochabel Soares Moretti3Victor Debbas4Tiphany Coralie De Bessa5Nathalia Tenguan Silva6Alexandre da Costa Pereira7Daniel Martins-de-Souza8Marcelo Larami Santoro9Francisco Rafael Martins Laurindo10Laboratorio de Biologia Vascular, LIM-64 (Biologia Cardiovascular Translacional), Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BrazilLaboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, Brazil; Instituto Nacional de Biomarcadores em Neuropsiquiatria (INBION), Conselho Nacional de Desenvolvimento Cientifico e Tecnologico, Sao Paulo, BrazilLaboratorio de Fisiopatologia, Instituto Butantan, Sao Paulo, 05503-900, BrazilLaboratorio de Biologia Vascular, LIM-64 (Biologia Cardiovascular Translacional), Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BrazilLaboratorio de Biologia Vascular, LIM-64 (Biologia Cardiovascular Translacional), Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BrazilLaboratorio de Biologia Vascular, LIM-64 (Biologia Cardiovascular Translacional), Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BrazilLaboratorio de Biologia Vascular, LIM-64 (Biologia Cardiovascular Translacional), Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BrazilLaboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of Sao Paulo Medical School Hospital, Sao Paulo, BrazilLaboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, Brazil; Instituto Nacional de Biomarcadores em Neuropsiquiatria (INBION), Conselho Nacional de Desenvolvimento Cientifico e Tecnologico, Sao Paulo, BrazilLaboratorio de Fisiopatologia, Instituto Butantan, Sao Paulo, 05503-900, BrazilLaboratorio de Biologia Vascular, LIM-64 (Biologia Cardiovascular Translacional), Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil; Corresponding author. Laboratorio de Biologia Vascular, LIM-64 (Biologia Cardiovascular Translacional), Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Av Eneas C Aguiar, 44 - Annex 2, 9th floor, CEP 05403-904, Sao Paulo, Brazil.Redox-related plasma proteins are candidate reporters of protein signatures associated with endothelial structure/function. Thiol-proteins from protein disulfide isomerase (PDI) family are unexplored in this context. Here, we investigate the occurrence and physiological significance of a circulating pool of PDI in healthy humans. We validated an assay for detecting PDI in plasma of healthy individuals. Our results indicate high inter-individual (median = 330 pg/mL) but low intra-individual variability over time and repeated measurements. Remarkably, plasma PDI levels could discriminate between distinct plasma proteome signatures, with PDI-rich (>median) plasma differentially expressing proteins related to cell differentiation, protein processing, housekeeping functions and others, while PDI-poor plasma differentially displayed proteins associated with coagulation, inflammatory responses and immunoactivation. Platelet function was similar among individuals with PDI-rich vs. PDI-poor plasma. Remarkably, such protein signatures closely correlated with endothelial function and phenotype, since cultured endothelial cells incubated with PDI-poor or PDI-rich plasma recapitulated gene expression and secretome patterns in line with their corresponding plasma signatures. Furthermore, such signatures translated into functional responses, with PDI-poor plasma promoting impairment of endothelial adhesion to fibronectin and a disturbed pattern of wound-associated migration and recovery area. Patients with cardiovascular events had lower PDI levels vs. healthy individuals. This is the first study describing PDI levels as reporters of specific plasma proteome signatures directly promoting contrasting endothelial phenotypes and functional responses. Keywords: Protein disulfide isomerase, Plasma proteome, Endothelial cells, Plasma protein signatures, Thiol proteinshttp://www.sciencedirect.com/science/article/pii/S2213231719300217 |
| spellingShingle | Percíllia Victória Santos de Oliveira Sheila Garcia-Rosa Ana Teresa Azevedo Sachetto Ana Iochabel Soares Moretti Victor Debbas Tiphany Coralie De Bessa Nathalia Tenguan Silva Alexandre da Costa Pereira Daniel Martins-de-Souza Marcelo Larami Santoro Francisco Rafael Martins Laurindo Protein disulfide isomerase plasma levels in healthy humans reveal proteomic signatures involved in contrasting endothelial phenotypes Redox Biology |
| title | Protein disulfide isomerase plasma levels in healthy humans reveal proteomic signatures involved in contrasting endothelial phenotypes |
| title_full | Protein disulfide isomerase plasma levels in healthy humans reveal proteomic signatures involved in contrasting endothelial phenotypes |
| title_fullStr | Protein disulfide isomerase plasma levels in healthy humans reveal proteomic signatures involved in contrasting endothelial phenotypes |
| title_full_unstemmed | Protein disulfide isomerase plasma levels in healthy humans reveal proteomic signatures involved in contrasting endothelial phenotypes |
| title_short | Protein disulfide isomerase plasma levels in healthy humans reveal proteomic signatures involved in contrasting endothelial phenotypes |
| title_sort | protein disulfide isomerase plasma levels in healthy humans reveal proteomic signatures involved in contrasting endothelial phenotypes |
| url | http://www.sciencedirect.com/science/article/pii/S2213231719300217 |
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