Abstract
Activated protein C (APC) promotes angiogenesis and reepithelialisation and accelerates healing of diabetic ulcers. The aim of this study was to determine the relationship between the incidence of lower leg ulcers and plasma levels of APC's precursor, protein C (PC), in diabetic patients. Patients with diabetes who had a lower leg ulcer(s) for >6 months (n = 36) were compared with age-, type of diabetes-, and sex-matched subjects with diabetes but without an ulcer (n = 36, controls). Total PC was assessed using a routine PC colorimetric assay. There was a significantly (P < 0.001) lower level of plasma PC in patients with ulcers (103.3 ± 22.7, mean ± SD) compared with control (127.1 ± 34.0) subjects, when corrected for age and matched for gender and type of diabetes. Ulcer type (neuropathic, ischaemic, or mixed) was not a significant covariate for plasma PC levels (P = 0.35). There was no correlation between PC levels and gender, type of diabetes, HbA1c, or C-reactive protein in either group. In summary, decreased circulating PC levels are associated with, and may predispose to, lower leg ulceration in patients with diabetes.
Highlights
Activated protein C (APC) is a plasma protease derived from its precursor, protein C (PC), which circulates in plasma at 3–5 μg/mL
APC exerts its cytoprotective effect through its receptor, endothelial protein C receptor (EPCR), which binds to both PC and APC with high affinity [5]
Biopsies taken immediately adjacent to chronic wounds in patients with diabetes exhibit very low total PC (PC plus APC) levels compared to normal skin [9]
Summary
Activated protein C (APC) is a plasma protease derived from its precursor, protein C (PC), which circulates in plasma at 3–5 μg/mL. Biopsies taken immediately adjacent to chronic wounds in patients with diabetes exhibit very low total PC (PC plus APC) levels compared to normal skin [9]. Total PC expression in skin surrounding lower leg ulcers in diabetic patients is lower than normal skin [9]. Taken together, these ndings triggered our hypothesis that low total PC levels may predispose to lower leg ulcers in. E aim of the present study was to determine if an association exists between circulating levels of total PC and lower leg ulcers in patients with diabetes Diabetes. e aim of the present study was to determine if an association exists between circulating levels of total PC and lower leg ulcers in patients with diabetes
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