RESUMEN
The purpose of this study was to determine the reliability of test results dependent upon blood and plasma sample stability when shipped by airfreight courier for reference laboratory assessment. Of particular interest was evaluation of von Willebrand profile assays and platelet dense granule storage pool analysis. Peripheral venous blood was obtained from healthy volunteers. von Willebrand factor (VWF) activity, VWF antigen, and factor VIII coagulant activity assays were performed immediately following venipuncture with additional aliquots of plasma frozen and stored at -70°C for subsequent analysis 48 hours later. One frozen aliquot was shipped via airfreight for analysis 48 hours later, with another frozen aliquot that remained on-site. Blood was also collected to enumerate platelet dense granules to determine whether shipment would affect results. Statistical analysis of all test results demonstrated significant correlation between immediately assayed samples and samples that were stored for 48 hours at -70°C ( P < .0001), or frozen and shipped on dry ice ( P < .0001) for analysis upon return to our laboratory. No difference was found in the mean number of platelet dense granules between samples retained in our laboratory or samples analyzed upon return of shipment ( P = .751).
Asunto(s)
Plaquetas/metabolismo , Conservación de la Sangre , Criopreservación , Vesículas Secretoras/metabolismo , Factor de von Willebrand/metabolismo , Femenino , Humanos , Masculino , Pruebas de Función PlaquetariaRESUMEN
BACKGROUND: Pulmonary arterial hypertension is a chronic lung disease associated with severe pulmonary vascular changes. A pathogenic role of oxidized lipids such as hydroxyeicosatetraenoic and hydroxyoctadecadienoic acids is well established in vascular disease. Apolipoprotein A-I mimetic peptides, including 4F, have been reported to reduce levels of these oxidized lipids and improve vascular disease. However, the role of oxidized lipids in the progression of pulmonary arterial hypertension and the therapeutic action of 4F in pulmonary arterial hypertension are not well established. METHODS AND RESULTS: We studied 2 different rodent models of pulmonary hypertension (PH): a monocrotaline rat model and a hypoxia mouse model. Plasma levels of hydroxyeicosatetraenoic and hydroxyoctadecadienoic acids were significantly elevated in PH. 4F treatment reduced these levels and rescued preexisting PH in both models. MicroRNA analysis revealed that microRNA-193-3p (miR193) was significantly downregulated in the lung tissue and serum from both patients with pulmonary arterial hypertension and rodents with PH. In vivo miR193 overexpression in the lungs rescued preexisting PH and resulted in downregulation of lipoxygenases and insulin-like growth factor-1 receptor. 4F restored PH-induced miR193 expression via transcription factor retinoid X receptor α. CONCLUSIONS: These studies establish the importance of microRNAs as downstream effectors of an apolipoprotein A-I mimetic peptide in the rescue of PH and suggest that treatment with apolipoprotein A-I mimetic peptides or miR193 may have therapeutic value.