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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Morris, TA; Marsh, JJ; Chiles, PG; Auger, WR; Fedullo, PF; Woods, VL

Published Date

  • June 1, 2006

Published In

Volume / Issue

  • 173 / 11

Start / End Page

  • 1270 - 1275

PubMed ID

  • 16514114

Pubmed Central ID

  • PMC2662971

International Standard Serial Number (ISSN)

  • 1073-449X

Digital Object Identifier (DOI)

  • 10.1164/rccm.200506-916OC


  • eng

Conference Location

  • United States