Lung Disease, Clinical And Experimental Studies

Background Pulmonary hypertension is a pathophysiologic syndrome with high mortality and disability. It is considered a pseudo-malignant tumor. Its exact mechanism is still not clear. Pulmonary hypertension is associated with intracellular membrane trafficking in which the protein Snap-23and Syntaxin-4are crucial. The aim of this study is to investigate the role of membrane trafficing associated proteins in the pathogenesis of pulmonary hypertension.Methods We create a membrane trafficking model in HPAEC (human pulmonary artery endothelial cells) by down regulation of Snap-23and Syntaxin-4gene expression.Using MTT to test the cell proliferation. The mRNA and protein level of membrane trafficking associated proteins (Snap-23, Syntaxin4,) and endothelial nitric oxide synthase, caveolin-1, bone morphogenic protein receptor II and PY-STAT3in cellular model were tested by reverse transcription-real time PCR and Western Blot. Also the apoptotic proteins caspase3,caspase8and caspase9were tested by Western Blot.Results In our cell model, compared to the control gruop, the proliferation and apoptosis of endothelial cells increased significantly. The expression of endothelial nitric oxide synthase, caveolin-1, bone morphogenic protein receptor II and PY-STAT3were decreased.Conclusions Down regulation of Snap-23and Syntaxin-4gene expression affects the proliferation and apoptosis of human pulmonary artery endothelial cells. Membrane trafficking associated proteins and endothelial nitric oxide synthase, caveolin-1and bone morphogenic protein receptor Ⅱ were involved in pathogenesis of pulmonary hypertension. Membrane trafficking dysfunction plays an important role in the pathogesis and progression of pulmonary hypertension. Introduction:Pulmonary embolism (pulmonary embolism, PE) is a clinical and pathophysiological syndrome of endogenous or exogenous embolism pulmonary artery caused by the pulmonary circulation disorders, including pulmonary thrombo-embolism (pulmonary thromboembolism PTE), fat embolism syndrome, amniotic fluid embolismair embolism, tumor embolism, which PTE is the most common type of PE. N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) is a predictor of adverse short-term clinical outcomes in patients with acute pulmonary embolism (APE), but its long-term prognostic value remains largely undefined. The aim of this study was to assess the value of plasma NT-proBNP with regard to recurrent venous thromboembolism (VTE).Materials and Methods:NT-proBNP levels were measured in224consecutive patients with the first episode of acute pulmonary embolism occurring from January2005to October2010. The symptomatic acute PE confirmed by objective examination was included, and the exclusion criteria were (1) congestive heart failure;(2) chronic obstructive pulmonary disease;(3) a prior documented episode of PE or DVT;(4) renal dysfunction; and (5) a life expectancy of less than6months. Patients were categorized into two groups by NT-proBNP reference range. Follow-ups were performed at3,6, and12months and yearly thereafter. The primary end point was symptomatic, recurrent fatal or nonfatal VTE.Results:NT-proBNP was elevated in158(70.5%) patients and not elevated in66(29.5%) patients. The age of the study population was60±14years (range,19-85years), and126(56.3%) patients were female. The patients with elevated NT-proBNP were older than patients with normal NT-proBNP level (age:62±14years and56±14years, P=0.004) and were more often accompanied with ECG abnormalities (27(17%) and4(7%), P=0.02) including right bundle branch block, atrial fibrillation and supraventricular tachycardia. Almost half of the study patients (110patients,49%) had hypertension. After a mean follow-up period of31.0±19.4months, patients with elevated NT-proBNP showed an increased risk of recurrent VTE (20patients,12.7%) compared to those without elevated NT-proBNP (only1patient,1.5%)(P=0.009). Of the7deaths related to pulmonary embolism,6occurred in patients with elevated NT-proBNP compared to patients with normal NT-proBNP (1of7deaths). In a multivariate analysis stratified by oral anticoagulant treatment duration, elevated NT-proBNP was an independent predictor of recurrent VTE (hazard ratio,10.50; P=0.02).Conclusions:Elevated NT-proBNP is associated with recurrent VTE in acute pulmonary embolism patients. Introduction:Pulmonary embolism (PE) represents a significant health concern because of its high morbidity and mortality and is moreover characterized by high rates of recurrence. It would be useful to know biomarkers that enable early identification of patients at high or low risk of primary and recurrent VTE. D-dimer can be used to exclude acute pulmonary embolism (PE) for its high negative predictive value (NPV). Also, it is a predictor of recurrent venous thromboembolism (VTE) after anticoagulation withdrawal. The aim of the present study was to assess the predictive value of D-dimer for recurrent VTE when tested at hospital discharge.Materials and Methods:Plasma D-dimer levels were repeatedly measured at hospital discharge in204consecutive patients with the first episode of acute pulmonary embolism. Patients were categorized to two groups by D-dimer levels at hospital discharge and followed up at3,6, and12months and yearly thereafter. The primary end point was symptomatic, recurrent fatal or nonfatal VTE.Results:D-dimer levels were persistently abnormal in66patients (32%). The age of the study population was60±14years (range,19-85years), and119(58%) patients were female. There were55(27%) acute PE patients in the study population that were considered to be provoked PE. After31±19months follow-up, patients with persistently abnormal D-dimer level levels showed a higher rate of of recurrent VTE (14patients,21%) compared to those with D-dimer regression (8patients,6%)(P=0.001). Fourteen (7%) patients died during follow up period. Of those,7deaths were related to PE, in which6occurred in patients with persistently abnormal D-dimer level, compared to the patients with D-dimer regression (only1death occurred in this group). However, PE-related death between two groups (P=0.08). Major bleeding events occurred in6patients (3%) and2bleedings were fatal. At the multivariate analysis, after adjustment for other relevant factors, persistently abnormal D-dimer level levels were an independent predictor of recurrent VTE in all subjects investigated,(hazard ratio,4.10;95%CI,1.61to10.39; P=0.003), especially in those with unprovoked PE (hazard ratio,4.61;95%CI,1.85to11.49; P=0.001). The negative predictive value of D-dimer was94.2%and92.9%in all subjects or those with unprovoked PE, respectively.Conclusions:Persistently abnormal D-dimer level levels at hospital discharge have a high negative predictive value for recurrence in patients with acute pulmonary embolism, especially in subjects with an unprovoked previous event.