We agree with Catrina and Brismar (1) that the main stimulus for hypoxia-inducible factor-1α (HIF-1α) is hypoxia. Thus, in view of the normal blood vessel density, one would not expect hypoxia, which would be compatible with the normal levels of HIF-1α observed in our subjects (2). We also agree that the situation may be different in chronic potentially hypoxic wounds.

With regard to our statement in the introduction that vascular endothelial growth factor levels are reduced in the skin of diabetic animals, this should actually read as follows: “in the skin wounds of diabetic animals.” This is in keeping with the correspondents’ comments, and in the conclusions we state that “the [vascular endothelial growth factor] expression is normally increased during the granulation phase of wound healing, and this response is diminished in diabetic mice” (3).

The aim of our study was to quantify the rate of wound healing in acute diabetic wounds in foot skin of humans and to examine its relationship to skin neurovascular function and structure. The most pertinent finding was the normal wound healing rate despite the significant functional and structural neurovascular abnormalities found.

Sergio-Bogdan C, Brismar K: Neurovascular factors in wound healing in the foot skin of type 2 diabetic subjects (Letter).
Diabetes Care
. DOI: 10.2337/dc07-1974
Krishnan STM, Quattrini C, Jeziorska M, Malik RA, Rayman G: Neurovascular factors in wound healing in the foot skin of type 2 diabetic subjects.
Diabetes Care
Frank S, Hubner G, Breier G, Longaker MT, Greenhalgh DG,Werner S: Regulation of vascular endothelial growth factor expression in cultured keratinocytes: implications for normal and impaired wound healing.
J Biol Chem