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VEGF‐C increases lymph pump flow in rat mesenteric microlymphatics
Author(s) -
Breslin Jerome W,
Wu Mack H,
Sun Hengrui,
Reynoso Rashell,
Yuan Sarah Y
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a279
Subject(s) - lymphangiogenesis , lymph , lymphatic system , extravasation , medicine , vascular permeability , contraction (grammar) , evans blue , pathology , endocrinology , metastasis , cancer
VEGF‐C is a well‐described promoter of lymphangiogenesis, however little is known about acute effects of VEGF‐C on lymphatic pump activity. We tested the hypothesis that VEGF‐C increases microlymphatic pump output. We examined rat mesenteric microlymphatics (approximately 75‐100 μm diameter) in vivo using intravital microscopy. Digital videos were recorded during baseline and at 1, 10, 20, 30, 45, and 60 minutes after treatment with 1 nM recombinant VEGF‐C (C156S). Contraction frequency, end diastolic diameter (EDD), end systolic diameter, stroke volume, and lymph pump flow (LPF) were determined at these time points. We also assessed arteriolar diameter and microvascular extravasation of FITC‐albumin. The results show that VEGF‐C significantly increased contraction frequency and EDD within one minute, and increased stroke volume and LPF at 10 minutes. These parameters remained elevated for 30 minutes. VEGF‐C did not significantly alter arteriolar diameter or microvascular permeability. Immunofluorescence staining revealed co‐localization of the VEGF‐C receptor, VEGFR‐3, with the lymphatic endothelial cell marker LYVE‐1. Taken together, the data 1) demonstrate that VEGF‐C increases microlymphatic pump output, and 2) provide evidence of endothelium‐associated regulation of microlymphatic phasic contractions and flow. Supported by NIH F32 HL76079, R01 HL61507, R01 HL70752, and R01 HL73324.