Prognostic value of markers of collagen remodeling in venous ulcers

Abstract

A 25 patient study was conducted into the relationship between markers of collagen metabolism in venous ulcer exudates and healing status, and their prognostic value in predicting healing performance. Wounds were sampled on at least 5 occasions over 12 months, the frequencies of which were determined by the need for clinic attendance. Specimens were taken from several sites on each ulcer using sterile preweighed filters. Wound margins were traced and sites recorded for each collection. Sample sites were evaluated for severity as improving, static, or deteriorating according to subsequent wound progression. Specimens were analyzed for levels of proenzyme and active forms of matrix metalloproteinases 2 and 9, neutrophil elastase, and type I collagen C propeptide. There was an overall trend of greater expression of all markers with increasing severity of wound site, this being highly significant for pro-matrix metalloproteinase-9 (p = 0.006). For samples collected simultaneously from improving and deteriorating regions of the same wound, paired data analysis showed statistically significant differences for pro-matrix metalloproteinase-9 (p < 0.001), neutrophil elastase (p < 0.005) and activated matrix metalloproteinase-9 (p < 0.05). Taken overall, these data show the potential of markers of collagen biochemistry as predictors of repair in venous ulcers; in particular pro-matrix metalloproteinase-9 and neutrophil elastase were found to be accurate prognostic indicators of subsequent healing.

Coping style and depression influence the healing of diabetic foot ulcers: observational and mechanistic evidence

“…Higher levels in unhealed patients indicate over-activity of MMP2, resulting in greater breakdown of the extracellular matrix, thus hindering healing [17]. Indeed, increased expression and/or activity of MMPs, including MMP2, has previously been observed in diabetic foot ulcers and venous ulcers, and related to healing status [18]. Our findings are therefore consistent with the notion that increased levels of MMP2 may contribute to the chronicity of diabetic foot ulcers.…”

“…Sterile, preweighed filter paper was applied to the wound to absorb fluid using methods described previously [18], and then reweighed and stored at −80°C until processing. Levels of MMPs were normalised to the mass of fluid collected.…”

“…We did not, therefore, predict the direction of this relationship. In contrast, increased levels of MMPs has been associated with ulcer chronicity [18]. We therefore predicted that MMP levels would be greater in patients whose ulcers remained unhealed at 24 weeks.…”

“…Salivary cortisol captures the activity of the hypothalamic-pituitary-adrenal axis (HPA), the primary system mediating the relationship between psychological distress and immunity. The MMPs 2 and 9 are markers and mediators of connective tissue remodelling (MMP-2) and inflammatory cell infiltration (MMP-9), and are known to be linked to healing of dermal ulcers [17,18]. Both the precursor (pro-MMP) and activated (act-MMP) forms of these enzymes were measured.…”

Androgens influence expression of matrix proteins and proteolytic factors during cutaneous wound healing

“…This neodermal tissue initially consists of type III and V collagens, fibronectin and proteoglycans, which are slowly replaced by collagen I (the most abundant collagen in uninjured dermis), itself gradually remodeled as the resultant scar tissue matures. In chronic, non-healing wounds, these processes are disturbed and excessive tissue breakdown results in the failure to accumulate sufficient amounts of several key matrix components as a result of both decreased rates of protein biosynthesis 33 and greatly increased proteolytic activity. 34 Intriguingly, male gender is the primary factor predisposing to chronic wound healing states in humans, 23 and our recent studies have demonstrated that androgens impair healing in mouse and human models.…”