Multi-Level Analysis of Adipose Tissue Reveals the Relevance of Perivascular Subpopulations and an Increased Endothelial Permeability in Early-Stage Lipedema
Lipedema is a chronic, progressive disease of adipose tissue with unknown etiology. Based on the relevance of the stromal vascular fraction (SVF) cell population in lipedema, we performed a thorough characterization of subcutaneous adipose tissue, SVF isolated thereof and the sorted populations of e...
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MDPI AG
2022-05-01
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| Online Access: | https://www.mdpi.com/2227-9059/10/5/1163 |
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| author | Karin Strohmeier Martina Hofmann Jaroslaw Jacak Marie-Sophie Narzt Marlene Wahlmueller Mario Mairhofer Barbara Schaedl Wolfgang Holnthoner Martin Barsch Matthias Sandhofer Susanne Wolbank Eleni Priglinger |
| author_facet | Karin Strohmeier Martina Hofmann Jaroslaw Jacak Marie-Sophie Narzt Marlene Wahlmueller Mario Mairhofer Barbara Schaedl Wolfgang Holnthoner Martin Barsch Matthias Sandhofer Susanne Wolbank Eleni Priglinger |
| author_sort | Karin Strohmeier |
| collection | DOAJ |
| description | Lipedema is a chronic, progressive disease of adipose tissue with unknown etiology. Based on the relevance of the stromal vascular fraction (SVF) cell population in lipedema, we performed a thorough characterization of subcutaneous adipose tissue, SVF isolated thereof and the sorted populations of endothelial cells (EC), pericytes and cultured adipose-derived stromal/stem cells (ASC) of early-stage lipedema patients. We employed histological and gene expression analysis and investigated the endothelial barrier by immunofluorescence and analysis of endothelial permeability in vitro. Although there were no significant differences in histological stainings, we found altered gene expression of factors relevant for local estrogen metabolism (aromatase), preadipocyte commitment (ZNF423) and immune cell infiltration (CD11c) in lipedema on the tissue level, as well as in distinct cellular subpopulations. Machine learning analysis of immunofluorescence images of CD31 and ZO-1 revealed a morphological difference in the cellular junctions of EC cultures derived from healthy and lipedema individuals. Furthermore, the secretome of lipedema-derived SVF cells was sufficient to significantly increase leakiness of healthy human primary EC, which was also reflected by decreased mRNA expression of VE-cadherin. Here, we showed for the first time that the secretome of SVF cells creates an environment that triggers endothelial barrier dysfunction in early-stage lipedema. Moreover, since alterations in gene expression were detected on the cellular and/or tissue level, the choice of sample material is of high importance in elucidating this complex disease. |
| first_indexed | 2024-03-10T03:16:34Z |
| format | Article |
| id | doaj.art-708005f6c1444639a328aadefc183929 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T03:16:34Z |
| publishDate | 2022-05-01 |
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| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-708005f6c1444639a328aadefc1839292023-11-23T10:11:58ZengMDPI AGBiomedicines2227-90592022-05-01105116310.3390/biomedicines10051163Multi-Level Analysis of Adipose Tissue Reveals the Relevance of Perivascular Subpopulations and an Increased Endothelial Permeability in Early-Stage LipedemaKarin Strohmeier0Martina Hofmann1Jaroslaw Jacak2Marie-Sophie Narzt3Marlene Wahlmueller4Mario Mairhofer5Barbara Schaedl6Wolfgang Holnthoner7Martin Barsch8Matthias Sandhofer9Susanne Wolbank10Eleni Priglinger11Ludwig Boltzmann Institute for Traumatology in Cooperation with the AUVA, 1200 Vienna, AustriaAustrian Cluster for Tissue Regeneration, 1200 Vienna, AustriaAustrian Cluster for Tissue Regeneration, 1200 Vienna, AustriaLudwig Boltzmann Institute for Traumatology in Cooperation with the AUVA, 1200 Vienna, AustriaLudwig Boltzmann Institute for Traumatology in Cooperation with the AUVA, 1200 Vienna, AustriaDepartment of Hematology and Internal Oncology, Johannes Kepler University, 4020 Linz, AustriaLudwig Boltzmann Institute for Traumatology in Cooperation with the AUVA, 1200 Vienna, AustriaLudwig Boltzmann Institute for Traumatology in Cooperation with the AUVA, 1200 Vienna, AustriaAustrian Center for Lipedema, Skin Aesthetic Vein Laser Practice, 4020 Linz, AustriaAustrian Center for Lipedema, Skin Aesthetic Vein Laser Practice, 4020 Linz, AustriaLudwig Boltzmann Institute for Traumatology in Cooperation with the AUVA, 1200 Vienna, AustriaLudwig Boltzmann Institute for Traumatology in Cooperation with the AUVA, 1200 Vienna, AustriaLipedema is a chronic, progressive disease of adipose tissue with unknown etiology. Based on the relevance of the stromal vascular fraction (SVF) cell population in lipedema, we performed a thorough characterization of subcutaneous adipose tissue, SVF isolated thereof and the sorted populations of endothelial cells (EC), pericytes and cultured adipose-derived stromal/stem cells (ASC) of early-stage lipedema patients. We employed histological and gene expression analysis and investigated the endothelial barrier by immunofluorescence and analysis of endothelial permeability in vitro. Although there were no significant differences in histological stainings, we found altered gene expression of factors relevant for local estrogen metabolism (aromatase), preadipocyte commitment (ZNF423) and immune cell infiltration (CD11c) in lipedema on the tissue level, as well as in distinct cellular subpopulations. Machine learning analysis of immunofluorescence images of CD31 and ZO-1 revealed a morphological difference in the cellular junctions of EC cultures derived from healthy and lipedema individuals. Furthermore, the secretome of lipedema-derived SVF cells was sufficient to significantly increase leakiness of healthy human primary EC, which was also reflected by decreased mRNA expression of VE-cadherin. Here, we showed for the first time that the secretome of SVF cells creates an environment that triggers endothelial barrier dysfunction in early-stage lipedema. Moreover, since alterations in gene expression were detected on the cellular and/or tissue level, the choice of sample material is of high importance in elucidating this complex disease.https://www.mdpi.com/2227-9059/10/5/1163lipedemaendothelial permeabilityendothelial cellspericytesstromal vascular fraction (SVF)adipose-derived stromal/stem cells (ASC) |
| spellingShingle | Karin Strohmeier Martina Hofmann Jaroslaw Jacak Marie-Sophie Narzt Marlene Wahlmueller Mario Mairhofer Barbara Schaedl Wolfgang Holnthoner Martin Barsch Matthias Sandhofer Susanne Wolbank Eleni Priglinger Multi-Level Analysis of Adipose Tissue Reveals the Relevance of Perivascular Subpopulations and an Increased Endothelial Permeability in Early-Stage Lipedema Biomedicines lipedema endothelial permeability endothelial cells pericytes stromal vascular fraction (SVF) adipose-derived stromal/stem cells (ASC) |
| title | Multi-Level Analysis of Adipose Tissue Reveals the Relevance of Perivascular Subpopulations and an Increased Endothelial Permeability in Early-Stage Lipedema |
| title_full | Multi-Level Analysis of Adipose Tissue Reveals the Relevance of Perivascular Subpopulations and an Increased Endothelial Permeability in Early-Stage Lipedema |
| title_fullStr | Multi-Level Analysis of Adipose Tissue Reveals the Relevance of Perivascular Subpopulations and an Increased Endothelial Permeability in Early-Stage Lipedema |
| title_full_unstemmed | Multi-Level Analysis of Adipose Tissue Reveals the Relevance of Perivascular Subpopulations and an Increased Endothelial Permeability in Early-Stage Lipedema |
| title_short | Multi-Level Analysis of Adipose Tissue Reveals the Relevance of Perivascular Subpopulations and an Increased Endothelial Permeability in Early-Stage Lipedema |
| title_sort | multi level analysis of adipose tissue reveals the relevance of perivascular subpopulations and an increased endothelial permeability in early stage lipedema |
| topic | lipedema endothelial permeability endothelial cells pericytes stromal vascular fraction (SVF) adipose-derived stromal/stem cells (ASC) |
| url | https://www.mdpi.com/2227-9059/10/5/1163 |
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