Dermal collagen and lipid deposition correlate with tissue swelling and hydraulic conductivity in murine primary lymphedema

Joseph M. Rutkowski, Carl Erik Markhus, Christina C. Gyenge, Kari Alitalo, Helge Wiig, Melody A. Swartz

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Primary lymphedema is a congenital pathology of dysfunctional lymphatic drainage characterized by swelling of the limbs, thickening of the dermis, and fluid and lipid accumulation in the underlying tissue. Two mouse models of primary lymphedema, the Chy mouse and the K14-VEGFR-3-Ig mouse, both lack dermal lymphatic capillaries and exhibit a lymphedematous phenotype attributable to disrupted VEGFR-3 signaling. Here we show that the differences in edematous tissue composition between these two models correlated with drastic differences in hydraulic conductivity. The skin of Chy mice possessed significantly higher levels of collagen and fat, whereas K14-VEGFR-3-Ig mouse skin composition was relatively normal, as compared with their respective wild-type controls. Functionally, this resulted in a greatly increased dermal hydraulic conductivity in K14-VEGFR3-Ig, but not Chy, mice. Our data suggest that lymphedema associated with increased collagen and lipid accumulation counteracts an increased hydraulic conductivity associated with dermal swelling, which in turn further limits interstitial transport and swelling. Without lipid and collagen accumulation, hydraulic conductivity is increased and overall swelling is minimized. These opposing tissue responses to primary lymphedema imply that tissue remodeling - predominantly collagen and fat deposition - may dictate tissue swelling and govern interstitial transport in lymphedema.

Original languageEnglish (US)
Pages (from-to)1122-1129
Number of pages8
JournalAmerican Journal of Pathology
Volume176
Issue number3
DOIs
StatePublished - Mar 2010

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Lymphedema
Collagen
Vascular Endothelial Growth Factor Receptor-3
Lipids
Skin
Fats
Lymphatic Vessels
Dermis
Drainage
Extremities
Pathology
Phenotype

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Dermal collagen and lipid deposition correlate with tissue swelling and hydraulic conductivity in murine primary lymphedema. / Rutkowski, Joseph M.; Markhus, Carl Erik; Gyenge, Christina C.; Alitalo, Kari; Wiig, Helge; Swartz, Melody A.

In: American Journal of Pathology, Vol. 176, No. 3, 03.2010, p. 1122-1129.

Research output: Contribution to journalArticle

Rutkowski, Joseph M. ; Markhus, Carl Erik ; Gyenge, Christina C. ; Alitalo, Kari ; Wiig, Helge ; Swartz, Melody A. / Dermal collagen and lipid deposition correlate with tissue swelling and hydraulic conductivity in murine primary lymphedema. In: American Journal of Pathology. 2010 ; Vol. 176, No. 3. pp. 1122-1129.
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