Tissue-specific endothelial cell heterogeneity contributes to unequal inflammatory responses
Abstract Endothelial cells (EC) coordinate vascular homeostasis and inflammation. In organ transplantation, EC are a direct alloimmune target. We posited that tissue specific heterogeneity of vascular EC may partly underlie the disparate organ-specific alloimmune risk. We examined the vascular endot...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-01-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-020-80102-w |
| _version_ | 1818851293270114304 |
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| author | Hasitha Gunawardana Tahmineh Romero Ning Yao Sebastiaan Heidt Arend Mulder David A. Elashoff Nicole M. Valenzuela |
| author_facet | Hasitha Gunawardana Tahmineh Romero Ning Yao Sebastiaan Heidt Arend Mulder David A. Elashoff Nicole M. Valenzuela |
| author_sort | Hasitha Gunawardana |
| collection | DOAJ |
| description | Abstract Endothelial cells (EC) coordinate vascular homeostasis and inflammation. In organ transplantation, EC are a direct alloimmune target. We posited that tissue specific heterogeneity of vascular EC may partly underlie the disparate organ-specific alloimmune risk. We examined the vascular endothelial response to inflammation across six primary endothelial beds from four major transplanted organs: the heart, lung, kidney and liver. First, we reanalyzed a public dataset of cardiac allograft rejection and found that endothelial inflammatory response genes were elevated in human cardiac allograft biopsies undergoing rejection compared with stable grafts. Next, the inducible inflammatory phenotypes of EC from heart, lung, kidney, and liver were characterized in vitro, focused on expression of adhesion molecules and chemokines, and recruitment of allogeneic peripheral blood mononuclear immune cells. Large vessel cardiac EC most highly upregulated VCAM-1, particularly compared with hepatic EC, supported greater leukocyte adhesion and had distinct chemokine profiles after stimulation with cytokines and complement. Differentially expressed gene candidates that are known regulators of cytokine signaling and inflammatory programming were verified in publicly available datasets of organ-specific endothelial transcriptomes. In summary, differential baseline expression of immune regulating genes may contribute to differential vascular inflammatory responses depending on organ. |
| first_indexed | 2024-12-19T07:02:43Z |
| format | Article |
| id | doaj.art-947d20a2137c4e92853281b5f4120750 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-19T07:02:43Z |
| publishDate | 2021-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-947d20a2137c4e92853281b5f41207502022-12-21T20:31:23ZengNature PortfolioScientific Reports2045-23222021-01-0111112010.1038/s41598-020-80102-wTissue-specific endothelial cell heterogeneity contributes to unequal inflammatory responsesHasitha Gunawardana0Tahmineh Romero1Ning Yao2Sebastiaan Heidt3Arend Mulder4David A. Elashoff5Nicole M. Valenzuela6Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los AngelesStatistics Core, David Geffen School of Medicine, University of CaliforniaStatistics Core, David Geffen School of Medicine, University of CaliforniaDepartment of Immunohaematology and Blood Transfusion, Leiden University Medical CenterDepartment of Immunohaematology and Blood Transfusion, Leiden University Medical CenterStatistics Core, David Geffen School of Medicine, University of CaliforniaDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los AngelesAbstract Endothelial cells (EC) coordinate vascular homeostasis and inflammation. In organ transplantation, EC are a direct alloimmune target. We posited that tissue specific heterogeneity of vascular EC may partly underlie the disparate organ-specific alloimmune risk. We examined the vascular endothelial response to inflammation across six primary endothelial beds from four major transplanted organs: the heart, lung, kidney and liver. First, we reanalyzed a public dataset of cardiac allograft rejection and found that endothelial inflammatory response genes were elevated in human cardiac allograft biopsies undergoing rejection compared with stable grafts. Next, the inducible inflammatory phenotypes of EC from heart, lung, kidney, and liver were characterized in vitro, focused on expression of adhesion molecules and chemokines, and recruitment of allogeneic peripheral blood mononuclear immune cells. Large vessel cardiac EC most highly upregulated VCAM-1, particularly compared with hepatic EC, supported greater leukocyte adhesion and had distinct chemokine profiles after stimulation with cytokines and complement. Differentially expressed gene candidates that are known regulators of cytokine signaling and inflammatory programming were verified in publicly available datasets of organ-specific endothelial transcriptomes. In summary, differential baseline expression of immune regulating genes may contribute to differential vascular inflammatory responses depending on organ.https://doi.org/10.1038/s41598-020-80102-w |
| spellingShingle | Hasitha Gunawardana Tahmineh Romero Ning Yao Sebastiaan Heidt Arend Mulder David A. Elashoff Nicole M. Valenzuela Tissue-specific endothelial cell heterogeneity contributes to unequal inflammatory responses Scientific Reports |
| title | Tissue-specific endothelial cell heterogeneity contributes to unequal inflammatory responses |
| title_full | Tissue-specific endothelial cell heterogeneity contributes to unequal inflammatory responses |
| title_fullStr | Tissue-specific endothelial cell heterogeneity contributes to unequal inflammatory responses |
| title_full_unstemmed | Tissue-specific endothelial cell heterogeneity contributes to unequal inflammatory responses |
| title_short | Tissue-specific endothelial cell heterogeneity contributes to unequal inflammatory responses |
| title_sort | tissue specific endothelial cell heterogeneity contributes to unequal inflammatory responses |
| url | https://doi.org/10.1038/s41598-020-80102-w |
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