Oxygen tension on the skin of the gaiter area of limbs with venous disease

Clyne, C. A. C.; Ramsden, William; Chant, A.D.B.; Webster, John H.

doi:10.1002/bjs.1800720820

Cited by 86 publications

(23 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Chronic venous ulcers share with diabetic ulcers the hypoxic environment (48) but not the exposure to high glucose levels. To test the in vivo relevance of our findings, we therefore analyzed HIF-1␣ protein levels in biopsy samples of diabetic and venous ulcers.…”

Section: Hif-1␣ Is Down-regulated By Hyperglycemiamentioning

confidence: 99%

Hyperglycemia Regulates Hypoxia-Inducible Factor-1α Protein Stability and Function

et al. 2004

View full text Add to dashboard Cite

Hyperglycemia and hypoxia are suggested to play essential pathophysiological roles in the complications of diabetes, which may result from a defective response of the tissues to low oxygen tension. In this study, we show that in primary dermal fibroblasts and endothelial cells, hyperglycemia interferes with the function of hypoxiainducible factor-1 (HIF-1), a transcription factor that is essential for adaptive responses of the cell to hypoxia. Experiments using proteasomal and prolyl hydroxylases inhibitors indicate that hyperglycemia inhibits hypoxiainduced stabilization of HIF-1␣ protein levels against degradation and suggest that mechanisms in addition to proline hydroxylation may be involved. This effect of hyperglycemia was dose dependent and correlates with a lower transcription activation potency of HIF-1␣, as assessed by transient hypoxia-inducible reporter gene assay. Regulation of HIF-1␣ function by hyperglycemia could be mimicked by mannitol, suggesting hyperosmolarity as one critical parameter. The interference of hyperglycemia with hypoxia-dependent stabilization of HIF-1␣ protein levels was confirmed in vivo, where only very low levels of HIF-1␣ protein could be detected in diabetic wounds, as compared with chronic venous ulcers. In conclusion, our data demonstrate that hyperglycemia impairs hypoxia-dependent protection of HIF-1␣ against proteasomal degradation and suggest a mechanism by which diabetes interferes with cellular responses to hypoxia. Diabetes 53:3226 -3232, 2004 C hronic complications of diabetes are a major health problem, and it has become a priority to characterize further their pathophysiological mechanisms to develop novel, rational therapeutic strategies. Even though prolonged exposure of the tissues to hyperglycemia seems to be the primary causative factor, some other factors may play a role as far as intensive blood glucose control reduces chronic complications but does not prevent them altogether (1,2). It has become increasingly evident that hypoxia plays an important role in all diabetes complications (3). In addition to deficient blood supply as a consequence of micro-and macrovascular disease, it has been postulated that hyperglycemia induces a pseudohypoxia state. This theory is based on the finding that high glucose concentrations induce a high NADH ϩ /NAD ϩ ratio in cells even when the oxygen tension is normal (4).Adaptive responses of cells to hypoxia are mediated by the hypoxia-inducible factor-1 (HIF-1), which is a heterodimeric transcription factor composed of two subunits, HIF-1␣ and aryl hydrocarbon receptor nuclear translocator (ARNT), both constitutively expressed in mammalian cells. Regulation of HIF-1 activity is critically dependent on the degradation of the HIF-1␣ subunit in normoxia. The molecular basis of its degradation is the O 2 -dependent hydroxylation of at least one of the two proline residues (5,6) in the oxygen-dependent degradation domain of HIF-1␣ by specific prolyl 4-hydroxylases (PHDs) (7-9). In this form, HIF-1 ␣ binds to the von Hippel-Lind...

show abstract

Section: Hif-1␣ Is Down-regulated By Hyperglycemiamentioning

confidence: 99%

Hyperglycemia Regulates Hypoxia-Inducible Factor-1α Protein Stability and Function

et al. 2004

View full text Add to dashboard Cite

show abstract

“…In contrast lymphatic regeneration does not occur in meshed skin transplants covering venous ulcers as an earlier study from our lab has shown [5]. The lack of lymphatic regeneration in 13 addition to a skin hypoxia in chronic venous insufficiency might explain the rather high recurrence rate of venous ulcers despite skin grafting and the increased risk of skin graft failure in venous ulcer [18] [19].…”

Section: Discussionmentioning

confidence: 79%

Microvascular regeneration in meshed skin transplants after severe burns

Meier¹,

Guggenheim²,

Vetter³

et al. 2011

Burns

View full text Add to dashboard Cite

Function of the skin lymphatics as well as blood perfusion of a meshed transplant is crucial for the healing. The lymphatic regeneration and arterial perfusion of skin transplants after severe burns of the extremities had been studied in eight patients by microlymphography, laser doppler perfusion imaging and transcutaneous oxygen pressure measurements 1, 6 and 18 months after transplantation. One month after transplantation, only fragmented as well as many giant lymphatic skin vessels were present in the transplant. After 6 months a normal lymphatic network had developed in all grafts. The extension of the dye in the lymphatics decreased from 4.5 (0-16) at 1 month to 3.0 (1-6) mm after 18 months, indicating improved lymph drainage capacity. The permeability of the lymphatics in the graft was normal. After 1 month, median laser flux in the transplant was 155.6% (105-246%) of the normal skin but it normalised within 18 months. By contrast, transcutaneous oxygen measurement (TcPO(2)) increased from 44 (21-47) to 55 (50-76) mmHg. In meshed transplants used to cover severely burned skin morphological and functional normal lymphatics develop within 6 months and the initially increased laser flux due to inflammatory reaction normalises. Our results provide important insights into the healing process of skin transplants after burn. (105-246%) of the normal skin but normalized within 18 months. In contrast, TcPO 2 increased from 44mmHg (21-47) to 55mmHg (50-76).In meshed transplants used to cover severely burned skin morphological and functional normal lymphatics develop within 6 months and the initially increased laser flux due to inflammatory reaction normalizes. Our results provide important insights in the healing process of skin transplants after burn.3 Introduction:

show abstract

“…Venous hypertension is not in itself sufficient cause for the development of CVI ulcers and there are several theories regarding the etiology of CVI ulcers. One school of thought suggests that local tissue ischemia induced by venous hypertension is responsible for venous ulcer pathogenesis [2][3][4][5][6][7]. Alternatively, recent investigations have focused attention on the involvement of inflammatory cells in the pathogenesis of CVI ulcers.…”

Section: Introductionmentioning

confidence: 99%