Compression‐induced HIF‐1 enhances thrombosis and PAI‐1 expression in mouse skin

Abstract Pressure ulcers result from tissue hypoxia caused by external forces. Thrombosis due to external forces is considered important, and hypoxia inducible factor‐1 (HIF‐1) is a master regulator of pressure ulcer development. To date, however, their causal relationship has not been determined. This study therefore investigated the mutual relationship between thrombosis and HIF‐1 activation in compressed mouse skin, based on a hypothesis that HIF‐1 regulation by plasminogen activator inhibitor‐1 (PAI‐1) enhances thrombosis. Compression of mouse skin significantly increased the numbers of thrombi and HIF‐1α‐positive cells compared with control skin. A thrombosis inhibitor significantly reduced the numbers of HIF‐1α‐positive cells and an HIF‐1 inhibitor significantly inhibited thrombosis in compressed skin tissue, suggesting a mutual relationship between thrombosis and HIF‐1 activation. Compression of mouse skin also enhanced the level of Pai‐1 messenger RNA expression, but this increase was significantly reduced by treatment with an HIF‐1 inhibitor, whereas a thrombosis inhibitor had no effect. These results suggested the involvement of PAI‐1 in HIF‐1‐enhanced thrombosis and that an additional factor participates in regulating Pai‐1 expression in compressed skin. These findings may suggest new strategies in pressure ulcer management.