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Updated: May 29, 2026
Assessment of Acute Wound Healing using the Dorsal Subcutaneous Polyvinyl Alcohol Sponge Implantation and Excisional Tail Skin Wound Models.
Published on: March 25, 2020
The influence of nitric oxide synthase 2 on cutaneous wound angiogenesis
L C Chin1, P Kumar, J A Palmer
1The O'Brien Institute and University of Melbourne, Department of Surgery at St Vincent's Hospital, 42 Fitzroy Street, Fitzroy, Vic. 3065, Australia.
Background:
Inducible nitric oxide synthase (nitric oxide synthase 2, NOS 2) inhibition significantly suppresses chronically ischaemic skin flap survival, possibly because of reduced angiogenesis.
Objectives:
To investigate the effect of genetic NOS 2 inhibition on cutaneous wound angiogenesis in two in vivo murine models. The impact of NOS 2 manipulation on vascular endothelial growth factor (VEGF)-A stimulated and fibroblast growth factor (FGF)-2 stimulated angiogenesis was also investigated in the Matrigel(®) plug assay.
Methods:
(i) Matrigel plugs/incisional wounds: two groups of NOS 2-/- mice and two groups of wild-type (WT) mice had bilateral Matrigel plugs containing 500 ng mL(-1) VEGF-A or 1000 ng mL(-1) FGF-2 injected subcutaneously in the abdomen. A 2·5 cm long dorsal incisional skin wound was created and sutured closed in the same animals. Wounds and plugs were explored at 7 or 12 days. (ii) Excisional wounds: dorsal 0·5 × 1·0 cm excisional skin wounds were created in four groups (two NOS 2-/- and two WT) and explored at 7 or 14 days. Wounds and Matrigel plugs were examined histologically and morphometrically for determination of percentage vascular volume (PVV).
Results:
The PVV in NOS 2-/- incisional wounds and excisional wounds was significantly less than in WT wounds (P = 0·05 and P < 0·001, respectively). The PVV was significantly less in VEGF-A stimulated Matrigel plugs compared with FGF-2 stimulated plugs in NOS 2-/- mice (P < 0·01), but not in WT mice.
Conclusions:
NOS 2 is significantly involved in angiogenic signalling in healing skin wounds, particularly within the first 7 days. However, Matrigel plug vascularization suggests that the role of NOS 2 in angiogenesis is related to VEGF-A but not FGF-2 stimulated angiogenesis.
Insights
Genetic inhibition of nitric oxide synthase 2 (NOS 2) impairs wound healing angiogenesis. NOS 2 plays a key role in vascular endothelial growth factor-A stimulated blood vessel growth but not fibroblast growth factor-2 stimulated growth.
Area of Science:
- Wound healing research
- Angiogenesis studies
- Molecular biology
Background:
- Inducible nitric oxide synthase 2 (NOS 2) inhibition reduces skin flap survival, potentially due to impaired angiogenesis.
- Understanding NOS 2's role in wound healing is crucial for improving regenerative therapies.
Purpose of the Study:
- To investigate the impact of genetic NOS 2 inhibition on cutaneous wound angiogenesis in vivo.
- To determine NOS 2's influence on vascular endothelial growth factor-A (VEGF-A) and fibroblast growth factor-2 (FGF-2) stimulated angiogenesis.
Main Methods:
- Utilized two murine models: Matrigel plugs and incisional/excisional skin wounds.
- Compared NOS 2 knockout (NOS 2-/-) mice with wild-type (WT) mice.
- Assessed vascularization using histological and morphometrical analysis of percentage vascular volume (PVV).
Main Results:
- NOS 2-/- mice exhibited significantly reduced PVV in both incisional and excisional wounds compared to WT mice.
- In NOS 2-/- mice, VEGF-A stimulated Matrigel plugs showed less vascularization than FGF-2 stimulated plugs.
- WT mice did not show a significant difference in vascularization between VEGF-A and FGF-2 stimulated plugs.
Conclusions:
- NOS 2 is critically involved in the angiogenic signaling of healing skin wounds, especially within the initial 7 days.
- The study suggests NOS 2's role in angiogenesis is specific to VEGF-A stimulation, not FGF-2.
- Genetic manipulation of NOS 2 impacts wound healing angiogenesis, highlighting its therapeutic potential.
Related Concept Videos
01:28Nitric Oxide Signaling Pathway
01:10Mechanism of Angiogenesis
01:24Regulation of Angiogenesis and Blood Supply
01:28Phases of Wound Repair
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