538Profilin-1 plasma levels are modulated by LPS induced disseminate intravascular coagulation

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Purpose: Disseminated intravascular coagulation (DIC) is a pathological condition derived from an excessive activation and stimulation of the coagulation system in which an excess of thrombin and fibrin deposition contribute to platelet aggregation provoking thrombotic microangiopaty. The objective of the present study was to determine whether profilin-1, a platelet protein secreted to plasma that we have found in STEMI patients is also released during DIC, a mayor platelet activator process.

Methods: DIC was induced in eight Wistar rats by administering an i.v. bolus injection of LPS (40 mg/Kg). Blood samples taken previous to the treatment (basaline), and 280 minutes after LPS administration (LPS) were used to evaluate circulating fibrinogen (von Clauss method) and to measure polymerized fibrinogen/fibrin formation (FIBTEM-assay). Western blot analysis was performed to evaluate Pfn-1 content in basal and LPS plasma samples. In vitro generated clots were analyzed by immunofluorecence techniques to elucidate the distribution of Pfn-1 within the in vitro clot and to quantify the amount of fibrinogen in basal and LPS samples.

Results: LPS treated rats present a highly significant reduction in fibrinogen levels (von Clauss method and confocal microscopy) and thromboelastograms in FIBTEM-assay showed a typical DIC profile. Western blot analysis showed a significant increase of Pfn-1 plasma levels after LPS treatment comparing with basal condition (P<0.05). In addition confocal images revealed a differential distribution of Pfn-1 before and after DIC. Pfn-1 was mostly associated with platelet at baseline and lost from platelets after LPS.

Conclusions: Our results show a clear relation between the activated state of circulating platelets and the levels of secreted Pfn-1 in the systemic circulation. The increase of Pfn-1 plasma levels in association with disseminated intravascular coagulation supports the potential role of Pfn-1 as a novel biomarker of ongoing thrombosis.

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