Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 196, Issue 11, Pages 1497-1506Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20021244
Keywords
VEGF-C; VEGF-D; PIGF; VPF/VEGF; VEGF-A
Categories
Funding
- NCI NIH HHS [P01 CA 92644, CA 69184, R01 CA050453, R01 CA069184, CA 50453, P01 CA092644, CA 91861, R01 CA086410] Funding Source: Medline
- NHLBI NIH HHS [HL 59316] Funding Source: Medline
- NIAID NIH HHS [R01 AI033372, AI 44066, AI 33372] Funding Source: Medline
Ask authors/readers for more resources
Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF, VEGF-A) is a multifunctional cytokine with important roles in pathological angiogenesis. Using an adenoviral vector engineered to express murine VEGF-A(164), we previously investigated the steps and mechanisms by which this cytokine induced the formation of new blood vessels in adult immunodeficient mice and demonstrated that the newly formed blood vessels closely resembled those found in VEGF-A-expressing tumors. We now report that, in addition to inducing angiogenesis, VEGF-A(164) also induces a strong lymphangiogenic response. This finding was unanticipated because lymphangiogenesis has been thought to be mediated by other members of the VPF/VEGF family, namely, VEGF-C and VEGF-D. The new giant lymphatics generated by VEGF-A(164) were structurally and functionally abnormal: greatly enlarged with incompetent valves, sluggish flow, and delayed lymph clearance. They closely resembled the large lymphatics found in lymphangiomas/lymphatic malformations, perhaps implicating VEGF-A in the pathogenesis of these lesions. Whereas the angiogenic response was maintained only as long as VEGF-A was expressed, giant lymphatics, once formed, became VEGF-A independent and persisted indefinitely, long after VEGF-A expression ceased. These findings raise the possibility that similar, abnormal lymphatics develop in other pathologies in which VEGF-A is overexpressed, e.g., malignant tumors and chronic inflammation.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available