Chemotherapy Research Today is a free monthly online journal that collates and summarizes the latest research about Chemotherapy, including details on cancer treatment, side effects, drugs.

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

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

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

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.

Published 1 June 2006 in Am J Respir Crit Care Med, 173(11): 1270-5.
Full-text of this article is available online (may require subscription).

© 2004-2008 Chemotherapy Research Today. All Rights Reserved.