The development and complications of diabetic foot ulcers

Laing, Peter

doi:10.1016/s0002-9610(98)00182-2

Cited by 104 publications

(65 citation statements)

References 27 publications

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“…The above results led us to investigate the effect of COMP-Ang1 on delayed cutaneous wound healing seen in diabetes, which is mainly caused by microangiopathy (6)(7)(8)(9). To do so, we made excisional full thickness wounds in the dorsal side of the tail, where contraction is minimal (23), of diabetic C57BLKS͞J-m ϩ͞ϩ Lepr db (db͞db) mice (24), whose phenotype resembles that of human adult-onset type II diabetes mellitus.…”

Section: Comp-ang1 Accelerates Wound Healing and Promotes Angiogenesismentioning

confidence: 99%

“…Delayed skin wound healing is a serious complication in diabetes and is caused primarily by microangiopathy and peripheral neuropathy accompanied by impaired cutaneous blood flow, hypoxia, accelerated inflammation, edema, and endothelial-neural dysfunction (6)(7)(8)(9). Moreover, expression of VEGF-A and Tie2, the angiopoietin-1 (Ang1) receptor, is markedly reduced in wounds in diabetes (10,11).…”

mentioning

confidence: 99%

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COMP-angiopoietin-1 promotes wound healing through enhanced angiogenesis, lymphangiogenesis, and blood flow in a diabetic mouse model

Cho

Sung

Kim

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

148

109

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Microvascular dysfunction is a major cause of impaired wound healing seen in diabetic patients. Therefore, reestablishment of structural and functional microvasculature could be beneficial to promote wound healing in these patients. Angiopoietin-1 (Ang1) is a specific growth factor functioning to generate a stable and functional vasculature through the Tie2 and Tie1 receptors. Here we determined the effectiveness of cartilage oligomeric matrix protein (COMP)-Ang1, a soluble, stable, and potent form of Ang1, on promotion of healing in cutaneous wounds of diabetic mice. An excisional full-thickness wound was made in the dorsal side of the tail of diabetic ( db / db ) mice, and mice were then treated systemically with adenovirus (Ade) encoding COMP-Ang1 or with control virus encoding β-gal (Ade-β-gal) or treated topically with recombinant COMP-Ang1 protein or BSA. Time course observations revealed that mice treated with Ade-COMP-Ang1 or COMP-Ang1 protein showed accelerated wound closure and epidermal and dermal regeneration, enhanced angiogenesis and lymphangiogenesis, and higher blood flow in the wound region compared with mice treated with control virus or BSA. COMP-Ang1 promotion of wound closure and angiogenesis was not dependent on endothelial nitric oxide synthase or inducible nitric oxide synthase alone. Taken together, these findings indicate that COMP-Ang1 can promote wound healing in diabetes through enhanced angiogenesis, lymphangiogenesis, and blood flow.

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Section: Comp-ang1 Accelerates Wound Healing and Promotes Angiogenesismentioning

confidence: 99%

mentioning

confidence: 99%

COMP-angiopoietin-1 promotes wound healing through enhanced angiogenesis, lymphangiogenesis, and blood flow in a diabetic mouse model

Cho

Sung

Kim

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

148

109

View full text Add to dashboard Cite

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“…39 From the above considerations, it follows that local treatment of wounds with VEGF protein or through VEGF gene transfer might represent an important tool to promote efficient wound repair, especially in conditions in which the physiological healing process is impaired, such as in diabetes. 40 As far as treatment with the VEGF protein is concerned, animal experiments and clinical trials have indicated that large, often repeated doses of growth factor are required to attain clinical benefit, suggesting that exogenous presentation can lead to clearance, sequestration 41 or destruction 42 of the factor. In contrast, gene transfer might overcome the shortcomings of direct application of the growth factor and promote sustained production and release of the growth factor within the wound site.…”

Section: Discussionmentioning

confidence: 99%

Recombinant AAV vector encoding human VEGF165 enhances wound healing

et al. 2002

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“…Diabetes is one of the major predisposing factors for the development of nonhealing skin wounds, particularly in the lower extremities (10). Although repeated episodes of ischemia/reperfusion injury are thought to be the proximal cause of most wounds in the feet of patients with diabetes, decreased vascular function and loss of peripheral sensory perception constitute underlying risk factors.…”

Section: Discussionmentioning

confidence: 99%

All-trans Retinoic Acid Improves Structure and Function of Diabetic Rat Skin in Organ Culture

et al. 2002

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Diabetes increases susceptibility to chronic ulceration. The cause of chronic wound formation in diabetic individuals is multifactorial but may be accelerated by changes in the structure and function of the skin secondary to impaired fibroblast proliferation, decreased collagen synthesis, and increased matrix metalloproteinase (MMP) expression. This study explored cellular and biochemical changes in organ cultures of skin from streptozotocin-diabetic (STZ-D) rats and the effects of all-trans retinoic acid (RA) on these changes. STZ-D rats were killed after 6 weeks. The skin was cut into 2-mm pieces and incubated in organ culture for 3 or 6 days in the absence or presence of 3 mol/l RA. After organ culture incubation, control and RA-treated tissue was examined histologically after staining with hematoxylin and eosin. In parallel, organ culture-conditioned medium was assayed for MMPs. Additional organ cultures were examined for collagen synthesis using 3 H-proline incorporation into trichloroacetic acid-precipitable material and for glycosaminoglycan production based on interaction with the cationic dye 1,9-dimethylmethylene blue and by staining of tissue sections with periodic acid Schiff reagents. Skin from 6-week STZ-D rats demonstrated features of dermal atrophy including thinning and disorganization of connective tissue bundles and increased space between bundles. The addition of RA resulted in cellular reactivation and partially reversed the histological features of dermal atrophy. Levels of latent and active MMP-9 and MMP-13 were elevated 4-and 10-fold, respectively, in STZ-D skin and reduced by 50 -75% (P < 0.05) by RA. Collagen synthesis was increased by 30% (P < 0.05) by RA, whereas glycosaminoglycan expression was increased by only 9% (NS). RA also increased proliferation of STZ-D skin fibroblasts (approximately threefold over control; P < 0.05). Together, these data suggest that RA has the capacity to improve structure and function of diabetic skin. Diabetes 51: 3510 -3516, 2002

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The development and complications of diabetic foot ulcers

Cited by 104 publications

References 27 publications

COMP-angiopoietin-1 promotes wound healing through enhanced angiogenesis, lymphangiogenesis, and blood flow in a diabetic mouse model

COMP-angiopoietin-1 promotes wound healing through enhanced angiogenesis, lymphangiogenesis, and blood flow in a diabetic mouse model

Recombinant AAV vector encoding human VEGF165 enhances wound healing

All-trans Retinoic Acid Improves Structure and Function of Diabetic Rat Skin in Organ Culture

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