[ Diabetes Solutions ]

Understanding Aspirin’s effect on wound healing offers hope for treating chronic wounds

Non-healing wounds associated with cardiovascular disease, aging, and diabetes are a major global healthcare issue. Diminished peripheral blood flow and decreased local neovascularization are critical factors that contribute to the delayed or nonhealing wounds in these patients. We have examined the dynamics of Cx expression during wound healing in diabetic rats, which is known to be slow. Results In diabetic wound tissues, the inducible nitric oxide synthase (iNOS) was activated, silent information regulator 1 (SIRT1) and forkhead box O transcription factor 1 (FoxO1) were elevated. STZ-treated WT mice, but not STZ-treated VEGFR1 TK(-/-) mice, showed accelerated wound healing when treated with placenta growth factor. Interestingly, all phases of the healing process are hindered in denervated tissue, and the mechanisms seem to be unrelated to those involved in vasculopathy or metabolic disorders like diabetes mellitus.6 Thus, neuropathy may affect each or a combination of the sensory, autonomic, and motor nervous systems. In small amounts, stress can be a life-saving thing.

Wounds (5 mm in diameter) were treated topically three times daily with 10−5 M NTX or sterile saline dissolved in cream and photographed every 2 days. However, Ang-1 gene transfer did not modify the decrease in VEGF mRNA and protein expression in diabetic mice; in contrast, Ang-1 increased eNOS expression and augmented nitrate wound content and VEGFR-2 immunostaining and protein expression. To see whether diabetes primes neutrophils to produce NETs, Wagner, Wong and colleagues at Joslin Diabetes Center and Pennsylvania State University examined neutrophils from patients with either type 1 or type 2 diabetes, finding that the cells contained four times the normal amount of PAD4 (a key enzyme in the NET production process) and made more NETs when stimulated. The intracellular actions of TGF β1 were studied by TEM. A higher cell proliferation rate and a denser and more organized new extracellular matrix and complete wound closure was detected at the 14th days in the TGF β1 treated wound in comparison with the 14th days for the untreated, control groups. “This study describes a novel mechanism for aspirin’s effect in delaying wound healing and suggests that aspirin should be used with caution in patients with chronic wounds,” says lead author Takehiko Yokomizo. Further work will be required to establish whether optimal treatment for wound healing might require a combination of approaches, such as BLT2 agonists together with growth factors to promote the number of wound-healing cells at the wound site, but this study offers hope that it may be possible to develop drugs that promote the healing of chronic wounds in humans.

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