Increased levels of VEGF-C and macrophage infiltration in lipedema patients without changes in lymphatic vascular morphology.


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
02 07 2020
Historique:
received: 19 02 2020
accepted: 15 06 2020
entrez: 4 7 2020
pubmed: 4 7 2020
medline: 2 12 2020
Statut: epublish

Résumé

Lipedema is a chronic adipose tissue disorder characterized by the disproportional subcutaneous deposition of fat and is commonly misdiagnosed as lymphedema or obesity. The molecular determinants of the lipedema remain largely unknown and only speculations exist regarding the lymphatic system involvement. The aim of the present study is to characterize the lymphatic vascular involvement in established lipedema. The histological and molecular characterization was conducted on anatomically-matched skin and fat biopsies as well as serum samples from eleven lipedema and ten BMI-matched healthy patients. Increased systemic levels of vascular endothelial growth factor (VEGF)-C (P = 0.02) were identified in the serum of lipedema patients. Surprisingly, despite the increased VEGF-C levels no morphological changes of the lymphatic vessels were observed. Importantly, expression analysis of lymphatic and blood vessel-related genes revealed a marked downregulation of Tie2 (P < 0.0001) and FLT4 (VEGFR-3) (P = 0.02) consistent with an increased macrophage infiltration (P = 0.009), without changes in the expression of other lymphatic markers. Interestingly, a distinct local cytokine milieu, with decreased VEGF-A (P = 0.04) and VEGF-D (P = 0.02) expression was identified. No apparent lymphatic anomaly underlies lipedema, providing evidence for the different disease nature in comparison to lymphedema. The changes in the lymphatic-related cytokine milieu might be related to a modified vascular permeability developed secondarily to lipedema progression.

Identifiants

pubmed: 32616854
doi: 10.1038/s41598-020-67987-3
pii: 10.1038/s41598-020-67987-3
pmc: PMC7331572
doi:

Substances chimiques

VEGFC protein, human 0
Vascular Endothelial Growth Factor C 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

10947

Références

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Auteurs

Gunther Felmerer (G)

Division of Plastic Surgery, Department of Trauma Surgery, Orthopaedics and Plastic Surgery, University Medical Center Göttingen, Georg-August-University, Göttingen, Germany.

Aikaterini Stylianaki (A)

Division of Plastic Surgery, Department of Trauma Surgery, Orthopaedics and Plastic Surgery, University Medical Center Göttingen, Georg-August-University, Göttingen, Germany.
Department for Plastic, Aesthetic and Hand Surgery, General Hospital Braunschweig, Brunswick, Germany.

Maija Hollmén (M)

MediCity Research Laboratory, University of Turku, Turku, Finland.

Philipp Ströbel (P)

Institute of Pathology, University Medical Center Göttingen, Georg-August-University, Göttingen, Germany.

Adam Stepniewski (A)

Division of Plastic Surgery, Department of Trauma Surgery, Orthopaedics and Plastic Surgery, University Medical Center Göttingen, Georg-August-University, Göttingen, Germany.

Anna Wang (A)

Department of Plastic Surgery and Hand Surgery, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland.

Florian S Frueh (FS)

Department of Plastic Surgery and Hand Surgery, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland.

Bong-Sung Kim (BS)

Department of Plastic Surgery and Hand Surgery, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland.

Pietro Giovanoli (P)

Department of Plastic Surgery and Hand Surgery, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland.

Nicole Lindenblatt (N)

Department of Plastic Surgery and Hand Surgery, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland.

Epameinondas Gousopoulos (E)

Department of Plastic Surgery and Hand Surgery, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland. epameinondas.gousopoulos@usz.ch.

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