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Am J Respir Crit Care Med. 2006 Jun 1;173(11):1270-5. Epub 2006 Mar 2.

Fibrin derived from patients with chronic thromboembolic pulmonary hypertension is resistant to lysis.

Author information

1
Division of Pulmonary/Critical Care Medicine, Department of Medicine, University of California, San Diego, CA 92103-8378, USA. t1morris@ucsd.edu

Abstract

RATIONALE:

Although acute pulmonary embolism is epidemiologically associated with chronic thromboembolic pulmonary hypertension, the factors responsible for resistance to thrombolysis and a shift toward vascular remodeling within the pulmonary arteries of patients with chronic thromboembolic pulmonary hypertension are unknown.

OBJECTIVE:

Determine whether fibrin from patients is more resistant to plasmin-mediated lysis than fibrin from healthy control subjects.

METHODS:

Fibrinogen purified from patients and control subjects was used to prepare fibrin clots, which were subsequently digested with plasmin for various periods of time. The degradation of the alpha-, beta-, and gamma-chains of fibrin and the appearance of peptide fragments over time were assessed by polyacrylamide gel electrophoresis and Western blotting.

MEASUREMENTS AND MAIN RESULTS:

Densitometry of Coomassie-stained gels revealed significantly slower cleavage of all three polypeptide chains of fibrin from patients compared with control subjects (p < 0.05). In particular, release of N-terminal fragments from the beta-chain of fibrin, which promote cell signaling, cell migration, and angiogenesis, was retarded in patients compared with control subjects (p < 0.01).

CONCLUSIONS:

The relative resistance of patient fibrin to plasmin-mediated lysis may be due to alterations in fibrin(ogen) structure affecting accessibility to plasmin cleavage sites. The persistence of structural motifs of fibrin, such as the beta-chain N-terminus, within the pulmonary vasculature could promote the transition from acute thromboemboli into chronic obstructive vascular scars.

PMID:
16514114
PMCID:
PMC2662971
DOI:
10.1164/rccm.200506-916OC
[Indexed for MEDLINE]
Free PMC Article
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