Proteomics of microparticles after experimental pulmonary embolism.

Abstract:

INTRODUCTION:Microparticles (MPs) are small fragments of apoptotic or activated cells that may contribute to pathological processes in cardiovascular diseases. In studies of MPs in clinical cohorts, it is unclear if observed changes in MP composition are a cause or a result of the cardiovascular disease being studied. The present studies employed a well-characterized rat model of experimental pulmonary embolism (PE) to determine if there were changes in MP characteristics as a result of pulmonary vascular occlusion. METHODS:PE was produced by infusing 25 μm polystyrene microspheres into the jugular vein of anesthetized rats. MPs were isolated by differential centrifugation of arterial blood 18 hr after PE. Proteins were separated by 1D gel electrophoresis and identified from tryptic digests by ultraperformance liquid chromatography (UPLC) coupled with tandem mass spectrometry. Statistical analysis was conducted using the Power Law Global Error Model (PLGEM). Changes in two proteins were confirmed by Western blot. RESULTS:Experimental PE produced pulmonary hypertension, mild systemic hypotension, hypoxia, hypercapnia and lactic acidosis. MPs showed significant elevation in proteins involved in clotting (fibronectin precursor, fibrinogen alpha, beta and gamma and von Willebrand factor) and several macroglobulin proteins, such as alpha-2-macroglobulin precursor compared with vehicle-treated control rats. Consistent with recent observations of hemolysis in PE, haptoglobin precursor protein, a major protein of hemoglobin clearance, decreased significantly in the PE animals. Plasma d-Dimer concentrations were significantly elevated, indicating that experimental PE produced a pro-coagulant state. CONCLUSIONS:These findings suggest that experimental PE produced significant, changes in MP characteristics to a prothrombotic phenotype.

journal_name

Thromb Res

journal_title

Thrombosis research

authors

Watts JA,Lee YY,Gellar MA,Fulkerson MB,Hwang SI,Kline JA

doi

10.1016/j.thromres.2011.09.016

subject

Has Abstract

pub_date

2012-07-01 00:00:00

pages

122-8

issue

1

eissn

0049-3848

issn

1879-2472

pii

S0049-3848(11)00503-2

journal_volume

130

pub_type

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