Multi-Level Analysis of Adipose Tissue Reveals the Relevance of Perivascular Subpopulations and an Increased Endothelial Permeability in Early-Stage Lipedema

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

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number1163
JournalBiomedicines
Volume10
Issue number5
DOIs
Publication statusPublished - 18 May 2022

Keywords

  • adipose tissue
  • adipose-derived stromal/stem cells (ASC)
  • aromatase
  • endothelial cells
  • endothelial permeability
  • lipedema
  • machine learning
  • pericytes
  • stromal vascular fraction (SVF)
  • ZNF423

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