Role of Skin Stretch on Local Vascular Permeability in Murine and Cell Culture Models.

Unlabelled: Excessive mechanical forces, particularly skin stretch, have been implicated in pathological cutaneous scarring. We hypothesize that this reflects, in part, stretch-induced vessel leakage that provokes prolonged wound/scar inflammation. However, this has never been observed directly. Here, a mouse model was used to examine the effect of skin flap stretching on vascular permeability. An in vitro model with pseudocapillaries grown in a stretchable chamber was also used to determine the effect of stretching on endothelial cell morphology and ion channel activity.

Methods: Murine skin flaps were stretched with a biaxial stretching device, after which FITC-conjugated-dextran was injected and imaged with fluorescence stereomicroscopy. Endothelial cells were induced to form pseudocapillary networks in an elastic chamber. The chamber was stretched and differential interference contrast microscopy was used to assess cell morphology. In other experiments, markers for Ca influx and K efflux were added before a single stretch was conducted. Histamine served as a positive-control in all experiments.

Results: Cyclic stretching (20%) increased the vascular permeability of skin flaps almost as strongly as histamine. Both stimuli also partially disrupted the pseudocapillary networks, induced cell contraction, and created gaps between the cells. Both stimuli caused sustained K efflux; stretching had a milder effect on Ca influx.

Conclusions: Excessive cyclical stretching strongly increased the vascular permeability of skin vessels and in vitro pseudocapillaries. This effect associated with increased K efflux and some Ca influx. Inhibiting such early stretch-induced signaling events may be an effective strategy for treating and preventing hypertrophic scars and keloids.