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Journal article
Predominant role of endothelial nitric oxide synthase in vascular endothelial growth factor-induced angiogenesis and vascular permeability
Proceedings of the National Academy of Sciences - PNAS, v 98(5), pp 2604-2609
27 Feb 2001
PMID: 11226286
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Nitric oxide (NO) plays a critical role in vascular endothelial
growth factor (VEGF)-induced angiogenesis and vascular
hyperpermeability. However, the relative contribution of different NO
synthase (NOS) isoforms to these processes is not known. Here, we
evaluated the relative contributions of endothelial and inducible NOS
(eNOS and iNOS, respectively) to angiogenesis and permeability of
VEGF-induced angiogenic vessels. The contribution of eNOS was assessed
by using an
eNOS-
deficient mouse, and iNOS contribution
was assessed by using a selective inhibitor
[
l
-
N
6
-(1-iminoethyl) lysine,
l
-NIL] and an
iNOS-
deficient mouse.
Angiogenesis was induced by VEGF in type I collagen gels placed in the
mouse cranial window. Angiogenesis, vessel diameter, blood flow rate,
and vascular permeability were proportional to NO levels measured with
microelectrodes: Wild-type (WT) ≥ WT with
l
-NIL or
iNOS
−/−
>
eNOS
−/−
≥
eNOS
−/−
with
l
-NIL. The role
of NOS in VEGF-induced acute vascular permeability increase in
quiescent vessels also was determined by using
eNOS-
and
iNOS-
deficient mice. VEGF superfusion significantly
increased permeability in both WT and
iNOS
−/−
mice but not in
eNOS
−/−
mice. These findings suggest that
eNOS plays a predominant role in VEGF-induced angiogenesis and vascular
permeability. Thus, selective modulation of eNOS activity is a
promising strategy for altering angiogenesis and vascular permeability
in vivo
.
Metrics
Details
- Title
- Predominant role of endothelial nitric oxide synthase in vascular endothelial growth factor-induced angiogenesis and vascular permeability
- Creators
- Dai Fukumura - Harvard UniversityTakeshi GohongiAnanth KadambiYotaro IzumiJennifer AngChae-Ok YunDonald G. BuerkPaul L. HuangRakesh K. Jain
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, v 98(5), pp 2604-2609
- Publisher
- The National Academy of Sciences
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000167258900090
- Scopus ID
- 2-s2.0-0035956947
- Other Identifier
- 991019231653004721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology