Time course of the angiogenic response during normotrophic and hypertrophic scar formation in humans

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Abstract
Previous research suggests that in hypertrophic scars (HSs), an excess of microvessels is present compared with normotrophic scars (NSs). The aim of our study was to quantify vascular densities in HSs and normotrophic scars and to provide an insight into the kinetics of changes in the expression of angiogenic factors in time during wound healing and HS formation. Human presternal wound healing after cardiothoracic surgery through a sternotomy incision was investigated in a standardized manner. Skin biopsies were collected at consecutive time points, i.e., during surgery and 2, 4, 6, 12, and 52 weeks postoperatively. The expression levels of angiopoietin‐1, angiopoietin‐2, Tie‐2, vascular endothelial growth factor, and urokinase‐type plasminogen activator were measured by real‐time reverse transcription‐polymerase chain reaction. Quantification of angiogenesis and cellular localization of the proteins of interest were based on immunohistochemical analysis. Microvessel densities were higher in the HSs compared with the normotrophic scars 12 weeks (p=0.017) and 52 weeks (p=0.030) postoperatively. Angiopoietin‐1 expression was lower in the hypertrophic group (pp=0.053), 12 weeks (ppp=0.008). Vascular endothelial growth factor expression was not significantly different when comparing both groups. In summary, the differential expression of angiopoietin‐1, angiopoietin‐2, and urokinase‐type plasminogen activator in time is associated with an increased vascular density in HSs compared with normotrophic scars.

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